SEARCH · PubMed Health

Results for “deacetylation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2001

Preparation of deacetyl-, lyso-, and deacetyl-lyso-GM(3) by selective alkaline hydrolysis of GM3 ganglioside.

Three methods (using GM3 quantities ranging from a few milligrams to grams) have been developed to prepare, in high yield, the three derivatives of ganglioside GM3 [alpha-Neu5Ac-(2-3)-beta-Gal-(1-4)-beta-Glc-(1-1)-ceramide]: deacetyl-GM3 [alpha-Neu-(2-3)-beta-Gal-(1-4)-beta-Glc-(1-1)-ceramide], lyso-GM3 [alpha-Neu5Ac-(2-3)-beta-Gal-(1-4)-beta-Glc-(1-1)-sphingosine], and deacetyl-lyso-GM3 [alpha-Neu-(2-3)-beta-Gal-(1-4)-beta-Glc-(1-1)-sphingosine]. This is the first report of the preparation of lyso-GM3 by a one-pot reaction. We can now define the optimal conditions for the different preparations. Preparation of deacetyl-GM3: alkaline reagent, 2 M KOH in water; GM3 concentration, 33 mg/ml; reaction temperature, 90 degrees C; reaction time, 3.5 h; nitrogen atmosphere. Preparation of deacetyl-lyso-GM3: alkaline reagent, 8 M KOH in water; GM3 concentration, 10 mg/ml; reaction temperature, 90 degrees C; reaction time, 18 h; nitrogen atmosphere. Preparation of lyso-GM(3): alkaline reagent, 1 M sodium tert-butoxide in methanol; GM3 concentration, 10 mg/ml; reaction temperature, 80 degrees C; reaction time, 18 h; anhydrous conditions. The percentage yield of deacetyl-GM3 was 70;-75%, that of deacetyl-lyso-GM3 100%, and of lyso-GM3 36;-40%.Deacetyl-GM3, deacetyl-lyso-GM3, and lyso-GM3 were purified by column chromatography, and chemical structures were confirmed by electron spray-mass spectrometry.

Chromatography, High Pressure Liquid↗

PubMed1989

A selective inhibitor of N8-acetylspermidine deacetylation in mice and HeLa cells without effects on histone deacetylation.

The inhibitory effects of 7-[N-(3-aminopropyl)amino]heptan-2-one (APAH) on N8-acetylspermidine deacetylation were studied. In in vitro studies, APAH produced inhibition (apparent Ki of 0.18 microM) of N8-acetylspermidine deacetylation by the 100,000g supernatant fraction of rat liver. This apparent Ki was 60-fold less than the apparent Km (11 microM) for deacetylation of the substrate, N8-acetylspermidine, suggesting that APAH could be a potent, effective inhibitor in vivo. APAH was administered to mice by intraperitoneal injection at a dose of 200 mg/kg, and polyamine and acetylpolyamine levels in liver and spleen were measured. In tissues of control mice, N8-acetylspermidine was not detectable but increased to detectable levels 30-360 min after APAH treatment. These data are consistent with inhibition of the deacetylase by APAH. Increases in putrescine and N1-acetylspermidine levels occurred in liver after APAH treatment with increases in N1-acetylspermidine levels observed in spleen. In HeLa cells, a significant increase in N8-acetylspermidine was observed following 24 h exposure to 10 microM APAH while no change occurred in the acetylation level of HeLa cell histones. In contrast, 24 h exposure to 10 mM sodium butyrate produced no change in N8-acetylspermidine levels and an increase in the acetylation level of histones H4 and H2B. These results suggest that APAH has a relatively selective inhibitory effect on N8-acetylspermidine but not histone deacetylation. This is the first report of significant levels of N8-acetylspermidine in animal tissues and of the effects of in vivo inhibition of N8-acetylspermidine deacetylase.

Acetylation↗

PubMed1980

Deacetylation of PS-5, a new beta-lactam compound, I. Microbial deacetylation of PS-5.

PS-5 was deacetylated to NS-5 (deacetylated PS-5) by l-amino acid acylase from porcine kidney and D-amino acid acylase from Streptomyces olivaceus but not by l-amino acid acylase from Aspergillus sp. Using PS-5, N-chloroacetyl-l-phenylalanine and N-chloroacetyl-D-valine as substrates, acylase producers were screened among facultative methanol-assimilating bacteria. Most of the microbes tested were active and could be classified into two groups of l-acylase producers and L-& D-acylase producers. Pseudomonas sp. 1158 which deacetylated the three substrates was chosen for further study. Cells of the bacterium entrapped in polyacrylamide gel and its acylase activities immobilized on DEAE-Sephadex were found to be useful for conversion of PS-5 to NS-5.

Acyltransferases↗

PubMed1997

In vitro and in vivo degradation of films of chitin and its deacetylated derivatives.

Chitin was deacetylated to various extents with NaOH to obtain partially and thoroughly deacetylated chitins. The specimens used in this study were deacetylated by 0 (chitin), 68.8, 73.3, 84.0, 90.1 and 100 mol% (chitosan). Films with a thickness of 150 microns were prepared from these specimens by the solution casting method. The equilibrated water contents of the films were 52.4 (chitin), 73.8 (68.8 mol%), 64.2 (73.3 mol%), 61.8 (84.0 mol%), 57.8 (90.1 mol%) and 49.7 wt% (chitosan), while the tensile strengths of the water-swollen films were 244 (chitin), 197 (68.8 mol%), 232 (73.3 mol%), 320 (84.0 mol%), 293 (90.1 mol%) and 433 g mm-2 (chitosan). The maximum water content and the minimum tensile strength observed for a specimen deacetylated between 0 and 68.8 mol% may be ascribed to the lowered crystallinity by deacetylation of chitin, since both chitin and chitosan are crystalline polymers. Unlike their physical properties, in vitro and in vivo degradations of these films occurred less rapidly without passing a maximum or minimum, as their degree of deacetylation became higher. The in vitro degradation was carried out by immersing the films in buffered aqueous solution of pH 7 containing lysozyme at 37 degrees C, while the in vivo degradation was studied by subcutaneously implanting the films in the back of rats. It was found that the rate of in vivo biodegradation was very high for chitin and 68.8 mol% deacetylated chitin, compared with that for the 73.3 mol% deacetylated chitin. The films which were more than 73.3 mol% deacetylated showed slower biodegradation. Interestingly, the tissue reaction towards highly deacetylated derivatives including chitosan was very mild, although they had cationic primary amines in the molecule.

Acetylation↗

PubMed2005

Mode of action on deacetylation of acetylated methyl glycoside by cellulose acetate esterase from Neisseria sicca SB.

The regioselective deacetylation of purified cellulose acetate esterase from Neisseria sicca SB was investigated on methyl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside and 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranoside. The substrates were used as model compounds of cellulose acetate in order to estimate the mechanism for deacetylation of cellulose acetate by the enzyme. The enzyme rapidly deacetylated at position C-3 of methyl 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside to accumulate 2,4,6-triacetate as the main initial reaction product in about 70% yield. Deacetylation was followed at position C-2, and generated 4,6-diacetate in 50% yield. The enzyme deacetylated the product at positions C-4 and C-6 at slower rates, and generated 4- and 6-monoacetates at a later reaction stage. Finally, it gave a completely deacetylated product. For 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranoside, CA esterase deacetylated at positions C-3 and C-6 to give 2,4,6- and 2,3,4-triacetate. Deacetylation proceeded sequentially at positions C-3 and C-6 to accumulate 2,4-diacetate in 55% yield. The enzyme exhibited regioselectivity for the deacetylation of the acetylglycoside.

Acetylation↗

PubMed2001

Structure-activity relationships in the deacetylation of O-glucosides of N-hydroxy-N-arylacylamides by mammalian liver microsomes.

Structure-activity relationships in the deacylation of O-glucosides of N-hydroxy-N-aryl-acylamides were investigated to provide insights into the metabolic activation of carcinogenic/mutagenic O-glycosides of N-hydroxy-N-arylacylamides. In the subcellular fractions obtained from porcine liver, the deacetylation activity toward O-glucoside of N-hydroxyacetanilide (GAc) was mainly localized in the microsomes. Both the 2-chloro (2ClGAc) and 2-methyl (2MeGAc) derivatives of GAc were not deacetylated by the microsomes. Other compounds having either 3- or 4-substituent (chloro or methyl), however, were deacetylated and showed higher V(max)/K(m) values than that of GAc. 4-Methyl derivative (4MeGAc) was shown to competitively inhibit the deacetylation activity toward GAc, and the K(i) value of 4MeGAc was comparable with its K(m) value obtained in the microsome-catalyzed deacetylation. These apparent K(m) values were shown to correspond to their lipophilicities estimated from retention times on high-performance liquid chromatography (HPLC). As for the effect of acyl groups, the order of V(max)/K(m) values was N-propionyl derivative (GPr)>GAc>N-butyryl derivative (GBu). From the optimized structures and energy levels of the frontier orbitals of these compounds, calculated by the semi-empirical AM1 method, the effects of 2-substituents and acyl groups on the deacetylation activity is thought to be due to a steric factor. From the energy levels of the frontier orbitals of GAc and its 3- or 4-substituted derivatives, the compound having a lower level of LUMO was shown to be deacetylated effectively. There were marked species differences in the microsomal deacetylation activity toward GAc, and the highest activity was found in the rabbit, followed by the porcine, hamster, rat and then bovine liver microsomes.

Aniline Compounds↗

PubMed1988

N- and O-deacetylation of N-acetoxy-N-arylacetamides by mammalian hepatic microsomes.

The present study demonstrates that hepatic microsomes from guinea pigs, rats, mice, hamsters, rabbits and dogs catalyze N-deacetylation of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-3,2'-dimethyl-4-acetylaminobiphenyl and O-deacetylation of N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) and N-acetoxy-3,2'-dimethyl-4-acetylaminobiphenyl (N-AcO-DMAABP). Gel filtration resolves the solubilized guinea pig microsomal enzymes into two deacetylases. The larger molecular weight enzyme catalyzes N-deacetylation of N-OH-AAF, whereas the smaller one cannot. Both enzymes catalyze O-deacetylation of N-AcO-AAF and N-AcO-DMAABP, but the activity is mainly due to the larger enzyme. Guinea pig and rat liver microsomes also catalyze N-deacetylation of N-AcO-AAF resulting in the binding of 2-aminofluorene to nucleic acids, but the activities are much less than that of the O-deacetylation of N-AcO-AAF. Thus, the amino-fluorene-DNA adducts which have been found in intact cells treated with N-AcO-AAF may result directly from N-deacetylation or indirectly from N,O-acetyltransfer following O-deacetylation.

Acetamides↗

PubMed1993

Regulation of glycosylphosphatidylinositol biosynthesis by GTP. Stimulation of N-acetylglucosamine-phosphatidylinositol deacetylation.

Glycosylphosphatidylinositol (GPI) is biosynthesized by the sequential addition of carbohydrates to phosphatidylinositol (PI). In the first two reactions, GlcNAc is transferred from UDP-GlcNAc to PI and then deacetylated to form GlcNAc-PI and GlcN-PI, respectively. In this paper, stimulation of GlcNAc-PI deacetylation by GTP, is reported. Addition of this nucleotide triphosphate to incubations in which GPI precursors were synthesized from UDP-[6-3H]GlcNAc by microsomes prepared from the lymphoma cell line EL4 resulted in a shift in the relative amount of each intermediate formed such that [6-3H]GlcN-PI was the predominant product. GTP also increased the total synthesis of the first GPI intermediate, GlcNAc-PI, by inhibiting reactions that metabolize UDP-[6-3H]GlcNAc into non-GPI-related products. However, unlike the stimulation of GlcNAc-PI deacetylation, ATP was equally effective in increasing the formation of GlcNAc-PI. An additional product, tentatively identified as [6-3H]GlcN-PI(acyl-inositol), was also detected when GTP was present in the incubation. The synthesis of this GPI precursor, which is proposed to be the third intermediate in GPI biosynthesis in mammals, was increased by GTP because the level of GlcN-PI, the substrate for acylation, was elevated. To isolate the effects of GTP on the GlcNAc-PI deacetylation, this reaction was studied directly by using [6-3H]GlcNAc-PI as the substrate. The stimulation was found to be specific for the guanosine-containing nucleotide triphosphate and optimal with approximately 1 mM GTP. Both the reaction rate at early time points and the total amount of deacetylated product formed in 60 min were increased by GTP. The effect on the second reaction of the pathway does not appear to be coupled to the first reaction because GlcNAc-PI deacetylation was increased by GTP in microsomes from cells defective in the GlcNAc-PI synthesis. Finally, 0.5 mM GTP gamma S (guanosine 5'-O-(thiotriphosphate)) completely inhibited the stimulation of GlcNAc-PI deacetylation caused by 1 mM GTP, indicating that hydrolysis of the nucleotide triphosphate was required for this effect. Although the mechanism and role of the GTP stimulation of GlcNAc-PI deacetylation is not clear, this regulation could influence the biosynthesis of mature GPI precursors and the subsequent expression of GPI-anchored proteins.

Acetylglucosamine↗

PubMed2003

Angiotensin I converting enzyme (ACE) inhibitory activity of hetero-chitooligosaccharides prepared from partially different deacetylated chitosans.

Angiotensin I converting enzyme (ACE) inhibitory activity of hetero-chitooligosaccharides (hetero-COSs) prepared from partially different deacetylated chitosans was investigated. Partially deacetylated chitosans, 90, 75, and 50% deacetylated chitosan, were prepared from crab chitin by N-deacetylation with 40% sodium hydroxide solution for durations. In addition, nine kinds of hetero-COSs with relatively high molecular masses (5000-10 000 Da; 90-HMWCOSs, 75-HMWCOSs, and 50-HMWCOSs), medium molecular masses (1000-5000 Da; 90-MMWCOSs, 75-MMWCOSs, and 50-MMWCOSs), and low molecular masses (below 1000 Da; 90-LMWCOSs, 75-LMWCOSs, and 50-LMWCOSs) were prepared using an ultrafiltration membrane bioreactor system. ACE inhibitory activity of hetero-COSs was dependent on the degree of deacetylation of chitosans. 50-MMWCOSs that are COSs hydrolyzed from 50% deacetylated chitosan, the relatively lowest degree of deacetylation, exhibited the highest ACE inhibitory activity, and the IC(50) value was 1.22 +/- 0.13 mg/mL. In addition, the ACE inhibition pattern of the 50-MMWCOSs was investigated by Lineweaver-Burk plots, and the inhibition pattern was found to be competitive.

Acetylation↗

PubMed1988

Histone acetylation in chicken erythrocytes. Rates of deacetylation in immature and mature red blood cells.

We analysed the rates of histone deacetylation in chicken mature and immature red blood cells. A multiplicity of deacetylation rates was observed for the histones and these rates may be subdivided into two major categories based on the extent of histone acetylation. In one set of experiments, cells were labelled with [3H]acetate in the presence of the deacetylase inhibitor n-butyrate, thereby accumulating radiolabel in the hyperacetylated forms of the histone. These hyperacetylated forms are deacetylated rapidly. [3H]Acetate-labelled tetra-acetylated H4 (H4Ac4) in mature cells was deacetylated with an initial half-life (t1/2) of approximately 5 min (time required for the removal of one-half of the labelled acetyl groups). In immature cells, all [3H]acetate-labelled H4Ac4 was deacetylated with a t1/2 of approximately 5 min. Erythrocytes were also labelled with [3H]acetate for extended periods in the absence of the deacetylase inhibitor. During this period, radiolabel accumulated predominantly in the mono- and di-acetylated forms of the histone. Using this protocol, the rate of deacetylation of H4Ac1 was observed to be approximately 145 min for mature cells, and approximately 90 min for immature cells, demonstrating that the less extensively acetylated histone is deacetylated slowly. These results are discussed in the context of the rates of histone acetylation in chicken red blood cells described in the companion paper [Zhang & Nelson (1988) Biochem. J. 250, 233-240].

Acetylation↗

PubMed1997

Deacetylation as a determinant of sulphonamide pharmacokinetics in pigs.

Sulphamonomethoxine (SMM), sulphadimidine (SDD), sulphadiazine (SDZ) and their N4-acetyl derivatives (AcSMM, AcSDD and AcSDZ) were intravenously injected into Goettingen miniature pigs and deacetylation was evaluated from plasma concentration-time curves, renal excretion, and rate constants obtained from pharmacokinetic analysis, using a non-linear least-squares method. Deacetylated metabolite was detected in both plasma and urine after intravenous injection of AcSMM, AcSDD and AcSDZ. The area under the curve (AUC) values for the deacetylated metabolite were significantly higher than those for acetyl derivatives after AcSMM and AcSDD administration, but significantly lower after AcSDZ. After AcSMM and AcSDD injection, the concentration ratio between deacetylated metabolite and acetyl derivative was almost constant in the terminal linear phase and similar to that seen after injection of sulphonamide. After AcSDZ injection, however, a constant ratio was not observed. These results indicate that deacetylation can have a significant effect on the pharmacokinetics of SMM and SDD, but not on those of SDZ in pigs. The rate constant for deacetylation was significantly higher than that for acetylation for SMM and SDD, but significantly lower for SDZ. It is, therefore, concluded that deacetylation may be a determinant of the pharmacokinetics of SMM and SDD in pigs. It was, however, not a determinant of SDZ pharmacokinetics because N4-acetylation is not the main elimination route in pigs.

Acetylation↗

PubMed2005

Gene expression analysis reveals that histone deacetylation sites may serve as partitions of chromatin gene expression domains.

BACKGROUND: It has been a long-term puzzle whether chromatin can be further divided into distinct gene expression domains. Because histone deacetylation affects chromatin structure, that in turn may affect the expression of nearby genes, histone deacetylation sites may act to partition chromatin into different gene expression domains. In this article, we explore the relationship between histone deacetylation sites and gene expression patterns on the genome scale using different data sources, including microarray data measuring gene expression levels, microarray data measuring histone deacetylation sites, and information on regulatory targets of transcription factors. RESULTS: Using 269 Saccharomyces cerevisiae microarray datasets, histone deacetylation datasets, and regulatory targets of transcription factors assembled from the Yeast Proteome Database and ChIP-chip data, we found that histone deacetylation sites can reduce the level of co-expression of neighboring genes. CONCLUSION: Histone deacetylation sites may serve as possible partition sites for chromatin domains and affect gene expression.

Binding Sites↗

PubMed2006

Activities of maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK) are not required for the global histone deacetylation observed after germinal vesicle breakdown (GVBD) in porcine oocytes.

The acetylation of nuclear core histone has been suggested to work as an epigenetic mark for transmitting gene expression patterns to daughter cells. Global histone deacetylations, presumably involved in the reprogramming of the gene expression, have been observed after germinal vesicle breakdown (GVBD) in a cell cycle-dependent manner during meiotic maturation of mouse and porcine oocytes, although the regulation mechanism of histone deacetylation has not been studied well. In the present study, we examined the involvement of a crucial cell-cycle-regulator, maturation-promoting factor (MPF), and a meiosis-related kinase, mitogen-activated protein kinase (MAPK), in the global histone deacetylation during porcine oocyte maturation. In order to know whether the activities of MPF and MAPK were required, or the breakdown of GV membrane was sufficient, for the global histone deacetylation observed after GVBD, we artificially destroyed the GV membrane of the porcine immature oocytes. The artificial GV destruction (AGVD) induced histone deacetylation without the activation of MPF and MAPK. This deacetylation after AGVD was not affected by an MPF inhibitor, roscovitine, or an inhibitor of protein synthesis, cycloheximide, but was completely prevented by an inhibitor of histone deactylases (HDACs), trichostatine A. HDAC1 was present in the GV of the immature oocytes and localized on chromosomes after GVBD and AGVD. These results suggest that the MPF and MAPK activities were dispensable and the breakdown of the GV membrane was sufficient for the global histone deacetylation, which was catalyzed by HDAC activity.

Acetylation↗

PubMed1988

Effects of N-deacetylation and N-desulfation of heparin on its anticoagulant activity and in vivo disposition.

This investigation compares the anticoagulant activities and in vivo disposition characteristics of N-deacetylated heparin and N-desulfated heparin with those of standard heparin in an animal model. The N-deacetylated heparin retained 23% of the anticoagulant activity, 34% of the anti-Xa activity and 23% of the anti-IIa activity of standard heparin, whereas the N-desulfated heparin retained only 1.5% of the anticoagulant activity, 0.095% of the anti-Xa activity and 0.92% of the anti-IIa activity of the original heparin. After i.v. injections of 5 mg/kg of the modified heparins, both N-deacetylated and N-deacetylated heparin concentrations showed monoexponential declines with time. The elimination half-lives were similar, 11.7 +/- 3.8 and 13.5 +/- 5.2 min, respectively (N.S.). There were, however, significant differences in both total clearance (Cl) and apparent volume of distribution (Vd) for these heparins, both parameters being significantly larger for the N-deacetylated heparin (P = .0007). The Cl values were 4.15 +/- 1.11 and 0.58 +/- 0.26 ml/min/kg and the Vd values were 72.1 +/- 38.7 and 9.9 +/- 2.4 ml/kg for the N-deacetylated and N-desulfated heparins, respectively. We have reported previously that after a similar dose of standard heparin the elimination half-life was 69.0 +/- 13.1 min, Cl was 0.64 +/- 0.16 ml/min/kg and Vd was 62.6 +/- 16.7 ml/kg. These studies have thus demonstrated that selective N-deacetylation and N-desulfation of the glucosamine residues of heparin affect markedly both its anticoagulant activity and in vivo disposition characteristics. Although important for full anticoagulant activity of heparin, the N-acetyl groups are apparently not essential.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

PubMed1984

In vitro deacetylation studies of acetamidophenolic compounds in rat brain, liver and kidney.

The in vitro deacetylation of ortho-, meta- and para-substituted acetophenetidines and acetamidophenols including acetanilide by arylacylamidases in rat brain, liver and kidney was investigated. In general, deacetylation rates were highest in liver and kidney preparations, whereas brain exhibited lower enzyme activities. Acetophenetidines were more suitable N-deacetylation substrates in comparison to acetamidophenols, whereby o-substituted compounds were split more easily than their corresponding m- or p-analogues. Among the arylacylamides tested, o-acetophenetidine was the predominant substrate in all tissues. It was deacetylated by far more rapidly than phenacetin. The enzymic deacetylation of acetophenetidines in kidney and brain was inhibited by p-nitrophenylacetate revealing that N-acetylamides as well as O-acetyl esters undergo similar degradation by carboxylesterase-amidases. The organophosphorous diester bis(p-nitrophenyl)-phosphate which is known to be a rather selective inhibitor of acetanilide-cleaving hydrolases in rat liver suppressed the deacetylation of acetanilide in all tissues investigated. In contrast to acetanilide, the deacetylation of acetophenetidines was inhibited by bis(p-nitrophenyl)-phosphate in liver and kidney, but bis(p-nitrophenyl)-phosphate was by far less active against acetophenetidine hydrolases in brain.

Acetamides↗

PubMed1991

Melatonin deacetylation: retinal vertebrate class distribution and Xenopus laevis tissue distribution.

Deacetylation is a rapid clearance mechanism for ocular melatonin. We have studied the distribution of retinal melatonin deacetylase activity among vertebrate classes. Exogenous radiolabeled melatonin is metabolized by ocular tissue prepared from the amphibian Xenopus laevis, the reptile Anolis carolinensis, the teleost fish Carassius auratus, and the bird Gallus domesticus. In contrast, we were unable to detect ocular melatonin breakdown in rat or pig. In each species exhibiting ocular melatonin breakdown, melatonin is first deacetylated to 5-methoxytryptamine, which is deaminated, producing 5-methoxyindoleacetic acid and 5-methoxytryptophol. Deacetylation of melatonin is inhibited by eserine (physostigmine), causing a reduction in the levels of all 3 metabolites. Deamination of 5-methoxytryptamine is inhibited by the monoamine oxidase inhibitor pargyline, such that 5-methoxyindoleacetic acid and 5-methoxytryptophol levels are decreased while levels of 5-methoxytryptamine are increased. Incubation with the deacetylase inhibitor eserine increases endogenous melatonin levels in Xenopus and Carassius eyecups, indicating that endogenous melatonin is metabolized via the deacetylase. We also studied the tissue distribution of the deacetylase in Xenopus laevis. Melatonin deacetylation occurs in retina, retinal pigment epithelium, and skin, all of which are sites of melatonin action. These results indicate that among non-mammalian vertebrates, deacetylation is a common clearance mechanism for ocular melatonin, and may degrade melatonin at other sites of action as well. Melatonin deacetylation may help regulate local melatonin concentration, and generates other biologically active methoxyindoles.

Amidohydrolases↗

PubMed2004

The effect of the degree of chitosan deacetylation on the efficiency of gene transfection.

Chitosans with various degrees of deacetylation were synthesized by acetylation with acetic anhydride. These chitosans were evaluated for efficacy of nanoparticle formation, DNA binding efficiency, morphology, and in vitro and in vivo gene transfection efficiency. DNA binding efficacy was reduced as degree of deacetylation was decreased, therefore requiring an increased +/-ratio to effect complete DNA complexation. For chitosan with a molecular weight of 390 kDa, the +/-ratio to achieve complete DNA complexation for degrees of deacetylation of 90%, 70% and 62% was 3.3:1, 5.0:1, and 9.0:1, respectively. The size and morphology of these nanoparticle formulations were not significantly different. The decreased degree of deacetylation results in a decrease in overall luciferase expression levels in HEK293, HeLa, and SW756 cells due to particle destabilization in the presence of serum proteins. However, intramuscular luciferase expression levels increased with decreasing deacetylation over the time points tested. Degree of chitosan deacetylation is an important factor in chitosan-DNA nanoparticle formulation as it affects DNA binding, release and gene transfection efficiency in vitro and in vivo.

Cell Line↗

PubMed1997

NMR and HPLC-NMR spectroscopic studies of futile deacetylation in paracetamol metabolites in rat and man.

HPLC-NMR spectroscopy has been used to investigate the level of deacetylation followed by reacetylation (futile deacetylation) of metabolites of paracetamol detected in human and rat urine. This has been achieved through the synthesis and administration of paracetamol isotopically labeled at the acetyl group with C2H3, 13CH3 and 13CO-13CH3. Using paracetamol-C2H3 it had been shown that in the rat the sulphate metabolite present in the urine shows 10-13% futile deacetylation depending on the dose, whereas for paracetamol-13CO-13CH3 the corresponding value was about 8%. After solid phase extraction, it was also possible to determine the level of futile deacetylation in the glucuronide metabolite using directly-coupled HPLC-NMR. This approach was facilitated by the use of acetonitrile-d3 as an HPLC eluent and the HPLC-NMR analyses showed that the level of futile deacetylation in the sulphate and glucuronide metabolites were equal at about 9%. The glucuronide of paracetamol-C2H3 was the predominant metabolite in man and following separation using HPLC-NMR, the level of futile deacetylation was shown to be 1% for the glucuronide and 2% for the sulphate, these values being equal within experimental error. This work demonstrates the utility of NMR and HPLC-NMR spectroscopy for isotope exchange studies.

Acetaminophen↗