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1.
Sheng Wu Gong Cheng Xue Bao ; 36(5): 861-867, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32567269

RESUMO

Lignocellulose is a major biomass resource for the production of biofuel ethanol. Due to its abundance, environmental friendliness and renewability, the utilization of lignocellulose is promising to solve energy shortage. Surfactant can effectively promote the enzymatic hydrolysis of lignocellulose. By discussing the influence and mechanism of different surfactants on the enzymatic hydrolysis, we provide references for finding appropriate surfactants in enzymatic hydrolysis process.


Assuntos
Lignina , Açúcares , Biocombustíveis , Biomassa , Hidrólise/efeitos dos fármacos , Lignina/metabolismo , Açúcares/metabolismo , Tensoativos/farmacologia
2.
J Pharmacol Sci ; 143(2): 127-131, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32156464

RESUMO

The inhibition of retinal ischemia-induced damage by post-ischemic prothymosin alpha (ProTα) was not affected in toll-like receptor 4 knockout (TLR4-/-) mice but blocked by the pretreatment with antibody against F0/F1 ATPase α- or ß-subunit, novel candidate for ProTα-receptor. In addition to the previous observation of ProTα-induced ATP release from cells, the present study showed a ProTα-induced enhancement of ATP hydrolysis activity of recombinant ATP5A1/5B complex. As the protection of retinal function by post-ischemic ProTα was abolished by anti-P2Y12 antibody, the activation of F0/F1 ATPase and subsequent P2Y12 receptor system may play roles in beneficial actions by post-ischemic ProTα.


Assuntos
Isquemia/metabolismo , Isquemia/prevenção & controle , Precursores de Proteínas/administração & dosagem , Precursores de Proteínas/farmacologia , ATPases Translocadoras de Prótons/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Retina , Timosina/análogos & derivados , Animais , Hidrólise/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Proteínas Recombinantes/metabolismo , Timosina/administração & dosagem , Timosina/farmacologia
3.
Lett Appl Microbiol ; 70(3): 181-188, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31784998

RESUMO

(R)-m-Nitrophenyl-1,2-ethanediol (m-NPED) is a versatile and highly value-added chiral building block for the synthesis of some bioactive compounds, such as (R)-Nifenalol. To efficiently produce (R)-m-NPED through the enantioconvergent hydrolysis of racemic (rac-) m-nitrostyrene oxide (m-NSO) using the whole resting cells of Escherichia coli/pCold-pveh2 intracellularly expressing PvEH2, an epoxide hydrolase from Phaseolus vulgaris, two reaction systems were investigated. In the Na2 HPO4 -NaH2 PO4 buffer (50 mmol l-1 , pH 7·0) system, merely 15 mmol l-1 rac-m-NSO was successfully subjected to enantioconvergent hydrolysis, producing (R)-m-NPED with 86·0% enantiomeric excess (eep ) and 177·6 mg l-1  h-1 space-time yield (STY). The experimental result indicated that there is inhibitory effect of rac-m-NSO at high concentration on PvEH2. To efficiently increase the concentration of rac-m-NSO and the STY of (R)-m-NPED, petroleum ether was first selected to construct an organic/aqueous two-phase system. Then, both the volume ratio (vo /vb ) of petroleum ether to phosphate buffer and the weight ratio (wc /ws ) of E. coli/pCold-pveh2 dry cells to rac-m-NSO were optimized as 2 : 8 and 5 : 1, respectively. In the optimized petroleum ether/phosphate buffer two-phase system, the enantioconvergent hydrolysis of rac-m-NSO at 40 mmol l-1 (6·6 mg ml-1 ) was carried out at 25°C for 12 h using 33·0 mg ml-1 vacuum freeze-dried cells of E. coli/pCold-pveh2, producing (R)-m-NPED with 87·4% eep , 82·3% yield and 502·4 mg l-1  h-1 STY. SIGNIFICANCE AND IMPACT OF THE STUDY: Epoxide hydrolases play a crucial role in producing enantiopure epoxides and/or vicinal diols. However, numerous biocatalytic reactions of organic compounds, such as epoxides, in aqueous phase suffered various restrictions. Herein, the enantioconvergent hydrolysis of rac-m-NSO in two reaction systems was investigated using the whole cells of Escherichia coli/pCold-pveh2. As a result, the concentration of rac-m-NSO and the space-time yield of (R)-m-NPED in organic/aqueous two-phase system were significantly increased, when compared with those in aqueous phase. To our knowledge, this is the first report about the production of (R)-m-NPED from rac-m-NSO at an elevated concentration by PvEH2 in the two-phase system.


Assuntos
Alcanos/química , Epóxido Hidrolases/metabolismo , Escherichia coli/metabolismo , Nitrocompostos/síntese química , Phaseolus/metabolismo , Biocatálise , Compostos de Epóxi , Hidrólise/efeitos dos fármacos , Phaseolus/enzimologia , Estereoisomerismo
4.
Chem Biol Interact ; 316: 108914, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31837295

RESUMO

Heroin (diamorphine) is a highly addictive opioid drug synthesized from morphine. The use of heroin and incidence of heroin associated overdose death has increased sharply in the US. Heroin is primarily metabolized via deacetylation (hydrolysis) forming the active metabolites 6-monoacetylmorphine (6-MAM) and morphine. A diminution in heroin hydrolysis is likely to cause higher drug effects and toxicities. In this study, we sought to determine the contribution of the major hepatic hydrolase carboxylesterase 1 (CES1) to heroin metabolism in the liver as well as the potential influence of one of its known genetic variants, G143E (rs71647871). Furthermore, given the potential therapeutic application of cannabidiol (CBD) for heroin addiction and the frequent co-abuse of cannabis and heroin, we also assessed the effects of CBD on heroin metabolism. In vitro systems containing human liver, wild-type CES1, and G143E CES1 S9 fractions were utilized in the assessment. The contribution of CES1 to the hydrolysis of heroin to 6-MAM was determined as 3.66%, and CES1 was unable to further catalyze 6-MAM under our assay conditions. The G143E variant showed a 3.2-fold lower intrinsic clearance of heroin as compared to the WT. CBD inhibited heroin and 6-MAM hydrolysis in a reversible manner, with IC50s of 14.7 and 12.1 µM, respectively. Our study results suggested only minor involvement of CES1 in heroin hydrolysis in the liver. Therefore, the G143E variant is unlikely to cause significant impact despite a much lower hydrolytic activity. CBD exhibited potent in vitro inhibition toward both heroin and 6-MAM hydrolysis, which may be of potential clinical relevance.


Assuntos
Canabidiol/farmacologia , Hidrolases de Éster Carboxílico/metabolismo , Hepatócitos/efeitos dos fármacos , Heroína/metabolismo , Hidrolases de Éster Carboxílico/química , Hidrolases de Éster Carboxílico/genética , Cromatografia Líquida de Alta Pressão , Hepatócitos/citologia , Hepatócitos/metabolismo , Heroína/análise , Humanos , Hidrólise/efeitos dos fármacos , Cinética , Polimorfismo de Nucleotídeo Único , Espectrometria de Massas em Tandem , Ácido Valproico/farmacologia
5.
Biochim Biophys Acta Gen Subj ; 1864(1): 129465, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676291

RESUMO

BACKGROUND: M20 aminopeptidases, such as Peptidase T (PepT), are implicated in the hydrolysis of oligopeptides during the terminal stages of protein degradation pathway to maintain turnover. Therefore, specific inhibition of PepT bores well for the development of novel next-generation antileishmanials. This work describes the metal dependence, substrate preferences and inhibition of PepT, and demonstrates in detail the role of its two conserved substrate binding residues. METHODS: PepT was purified and characterized using a scheme of peptide substrates and peptidomimetic inhibitors. Residues T364 and N378 were mutated and characterized with an array of biochemical, biophysical and structural biology methods. RESULTS: PepT sequence carries conserved motifs typical of M20 peptidases and our work on its biochemistry shows that this cytosolic enzyme carries broad substrate specificity with best cleavage preference for peptides carrying alanine at the P1 position. Peptidomimetics amastatin and actinonin occupied S1 pocket by competing with the substrate for binding to active site and inhibited PepT potently, while arphamenine A and bestatin were less effective inhibitors. We further show that the mutation of conserved substrate binding residues (T364 and N378) to alanine affects structure, reduces substrate binding and alters the amidolytic activity of this dimeric enzyme. CONCLUSIONS: PepT preferentially hydrolyzes oligopeptides carrying alanine at P1 position and is potently inhibited by peptidomimetics. Reduced substrate binding after mutations was a key factor involved in amidolytic digressions. GENERAL SIGNIFICANCE: This study provides insights for further exploration of the druggability of PepT and highlights prospective applications of this enzyme along with its mutazyme T364A/N378A.


Assuntos
Aminopeptidases/química , Leishmaniose/tratamento farmacológico , Oligopeptídeos/farmacologia , Peptidomiméticos/química , Sequência de Aminoácidos , Aminopeptidases/antagonistas & inibidores , Aminopeptidases/genética , Sítios de Ligação/efeitos dos fármacos , Humanos , Hidrólise/efeitos dos fármacos , Cinética , Leishmania/efeitos dos fármacos , Leishmania/enzimologia , Leishmania/patogenicidade , Leishmaniose/genética , Leishmaniose/parasitologia , Mutação/genética , Oligopeptídeos/química , Peptídeos/química , Peptídeos/farmacologia , Peptidomiméticos/farmacologia , Proteólise/efeitos dos fármacos , Especificidade por Substrato
6.
Molecules ; 24(24)2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31817934

RESUMO

Autophagy is an important self-degradative mechanism that plays a key role in treating neurodegeneration diseases. This research aimed at discovering bioactive compounds from Aster koraiensis. A new triterpene saponin, astersaponin I (1), was isolated from the EtOH extract of A. koraiensis. The structure of 1 was characterized by spectroscopic methods, ECD calculation, and acid hydrolysis. The biochemical analysis showed that compound 1 significantly increased the expression of microtubule-associated protein 1A/1B light chain 3B (LC3-II) expression in SH-SY5Y cells, which indicates the induction of autophagy. Thus, further study may be needed to clarify whether compound 1 exerts beneficial effects on neurodegeneration diseases like Parkinson's disease through autophagy induction.


Assuntos
Aster/química , Doença de Parkinson/tratamento farmacológico , Triterpenos/química , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hidrólise/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/genética , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Saponinas/química , Saponinas/farmacologia , Triterpenos/farmacologia
7.
Eur J Pharm Biopharm ; 145: 54-64, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31654712

RESUMO

To achieve enhanced cancer therapy, a sequentially dynamic polymeric drug delivery system (ortho ester-linked PEGylated poly(disulfide)s-based micelle-doxorubicin (PS-g-OEMPEG-DOX)) is successfully constructed. The PEGylated micelle can keep stable in sodium dodecyl sulfate (SDS) solution at pH 7.4, but be prone to DePEGylation and dynamic size changes via the hydrolysis of ortho ester linkages in side chains at tumoral extracellular pH value (6.5). Moreover, the micelle can rapidly release DOX via the cleavage of poly(disulfide)s in backbone at intracellular reductive milieu (10 mmol/L of dithiothreitol (DTT)). The dynamic micelle with detachable PEGylation achieves the stable blood circulation, improved cellular uptake and cytotoxicity, stronger in vitro penetration and inhibition of tumoral multicellular spheroids, and significant in vivo tumor accumulation and inhibition while decreasing side effects. Thus, the sequentially dynamic polymeric micelle with detachable PEGylation can be considered as a promising and effective drug delivery system in cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Ditiotreitol/administração & dosagem , Ditiotreitol/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Hidrólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Micelas , Dodecilsulfato de Sódio/química
8.
Mar Drugs ; 17(10)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623339

RESUMO

For full use of fish by-products, scale gelatin (TG) and antioxidant peptides (APs) of skipjack tuna (Katsuwonus pelamis) were prepared, and their properties were characterized using an amino acid analyzer, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy (FTIR), electrospray ionization mass spectrometers (ESI-MS), and radical scavenging assays. The results indicate that TG with a yield of 3.46 ± 0.27% contained Gly (327.9 ± 5.2 residues/1000 residues) as the major amino acid and its imino acid content was 196.1 residues/1000 residues. The structure of TG was more unstable than that of type I collagen from scales of skipjack tuna (TC) and TG was more suitable for preparation of hydrolysate by protease than mammalian gelatins. Therefore, TG was separately hydrolyzed under five proteases (pepsin, papain, trypsin, neutrase, and alcalase) and ten APs (TGP1-TGP10) were isolated from the alcalase-hydrolysate. Among them, TGP5, TGP7, and TGP9 with high antioxidant activity were identified as His-Gly-Pro-Hyp-Gly-Glu (TGP5), Asp-Gly-Pro-Lys-Gly-His (TGP7) and Met-Leu-Gly-Pro-Phe-Gly-Pro-Ser (TGP9), respectively. Furthermore, TGP5, TGP7, and TGP9 exhibited a high radical scavenging capability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (EC50 values of 1.34, 0.54, and 0.67 mg/mL, respectively), hydroxyl radical (EC50 values of 1.03, 0.41, and 0.74 mg/mL, respectively), and superoxide anion radical (EC50 values of 1.19, 0.71, and 1.59 mg/mL, respectively). These results suggest that three APs (TGP5, TGP7, and TGP9), especially TGP7, have a strong antioxidant activity and could act as potential antioxidant ingredients applied in functional products.


Assuntos
Antioxidantes/farmacologia , Gelatina/farmacologia , Peptídeos/farmacologia , Atum/metabolismo , Aminoácidos/metabolismo , Animais , Colágeno Tipo I/metabolismo , Depuradores de Radicais Livres/farmacologia , Hidrólise/efeitos dos fármacos , Radical Hidroxila/metabolismo , Superóxidos/metabolismo
9.
Food Chem Toxicol ; 133: 110731, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31369851

RESUMO

The effect of chitosan (CS) on the in vitro digestibility and molecular structural properties of lotus seed starch (LS), and the correlation matrix was studied. The addition of CS could delay the hydrolysis of LS due to a increased level of slowly digestible starch (SDS). LS-CS blends exhibited lower pasting viscosity, greater amylose content and higher ordered structure than LS alone. A significant correlation was found between the digestibility and molecular structural properties of LS-CS blends. Rapidly digestible starch content was positively correlated with viscosity and full width at half-maximum height (FWHH) at 480 cm-1; whereas, SDS content was negatively correlated with setback and FWHH. Moreover, CS concentration was positively related to absorbances at 1047 and 1035 cm-1and amylose content. The results indicated that the addition of CS could be beneficial to the formation of an ordered molecular structure in LS-CS blends and decreased digestibility in vitro.


Assuntos
Amilose/química , Quitosana/química , Amilose/análise , Calefação , Hidrólise/efeitos dos fármacos , Lotus/química , Estrutura Molecular , Sementes/química , Viscosidade
10.
Environ Sci Pollut Res Int ; 26(28): 29366-29378, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396876

RESUMO

The aim of this study was to improve the ethanol production from pomegranate peels (PPs). Therefore, the effect of enzymatic hydrolysis and different pretreatments on ethanol production by yeasts was examined. There were three different enzyme concentrations (3.6, 7.2, 14.4 FPU/g substrate) tested for enzymatic hydrolysis, and four different PP media, such as WSPP (whole slurry of PP), LFPP (liquid fraction of PP), WSFPP (washed solid fraction of PP) and N-WSFPP (non-washed solid fraction of PP), were prepared. Bioethanol production was monitored for 96 h. Maximum ethanol concentrations were obtained at WSPP medium as 12.69 g/L, 14.35 g/L and 4.23 g/L in Saccharomyces cerevisiae, Kluyveromyces marxianus and Pichia stipitis, respectively. On the other hand, the washing step of biomass increased the kinetic parameters dramatically and the highest theoretical ethanol yields and YP/S values were obtained from WSFPP medium in all tested yeasts. Theoretical ethanol yields were 97.8%, 98.7% and 35.5% for S. cerevisiae, K. marxianus and P. stipitis, respectively. Qp values were observed as 0.98 g/L h, 0.99 g/L h and 0.04 g/L h for the same yeasts. The highest YP/S values were detected as 0.50 g/g for S. cerevisiae, 0.50 g/g for K. marxianus and 0.30 g/g for P. stipitis in the washed pomegranate peel biomass.


Assuntos
Etanol/química , Lythraceae/química , Pichia/metabolismo , Romã (Fruta)/química , Saccharomyces cerevisiae/química , Biomassa , Etanol/metabolismo , Fermentação , Hidrólise/efeitos dos fármacos , Lythraceae/metabolismo , Pichia/química , Romã (Fruta)/metabolismo
11.
Int J Biol Macromol ; 139: 1141-1150, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31404603

RESUMO

A trypsin inhibitor was purified from the seeds of Psoralea corylifolia by ion-exchange and affinity chromatography. The purified fractions were subjected to RP- HPLC which resolved into a single peak. SDS-PAGE analysis gave an apparent molecular weight of 18 kDa. P. corylifolia trypsin inhibitor (PCTI) was found to be a competitive inhibitor and was active over a broad temperature (10-100 °C) and pH (6-11) range. It was shown to have a deleterious effect on growth and development of larvae of the melon fruit fly, Bactrocera cucurbitae, when incorporated in artificial diet using various concentrations. The larval, pupal, total development period and larval mortality significantly increased during the treatment. Inhibitory effects were also observed on percentage emergence which was significantly reduced. Nutritional indices namely food assimilated (FA) and mean relative growth rate (MRGR) also decreased significantly with increase in concentration of PCTI. qRT-PCR results indicated that the expression of trypsin and chymotrypsin genes were down-regulated while elastase, catalase, GST, SOD and AP were up-regulated. PCTI was also effective against certain bacterial strains. These results indicated that the peptidase inhibitor from P. corylifolia may be a potential bio-control agent which can decrease the damage caused by B. cucurbitae and other related destructive pests.


Assuntos
Antibacterianos/farmacologia , Psoralea/química , Sementes/química , Tephritidae/efeitos dos fármacos , Tephritidae/crescimento & desenvolvimento , Inibidores da Tripsina/farmacologia , Animais , Antibacterianos/isolamento & purificação , Bioensaio , Caseínas/metabolismo , Hidrólise/efeitos dos fármacos , Concentração Inibidora 50 , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Tephritidae/fisiologia , Inibidores da Tripsina/isolamento & purificação
12.
Drug Alcohol Depend ; 202: 168-171, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352306

RESUMO

BACKGROUND: Cocaine is a commonly abused drug and there is no approved medication specifically to treat its addiction or overdose. Bacterial cocaine esterase (CocE)-derived RBP-8000 is currently under clinical development for cocaine overdose treatment. It is proven to be effective for human use to accelerate cocaine metabolism into physiologically inactive products. Besides cocaine, RBP-8000 may hydrolyze the neurotransmitter acetylcholine (ACh), however, no study has reported its cholinesterase activity. The present study aims to examine RBP-8000's cholinesterase activity and substrate selectivity to address the potential concern that this enzyme therapy might produce cholinergic side-effects. METHODS: Both computational modeling and experimental kinetic analysis were carried out to characterize the potential cholinesterase activity of RBP-8000. Substrates interacting with RBP-8000 were modeled for their enzyme-substrate binding complexes. In vitro enzymatic kinetic parameters were measured using Ellman's colorimetric assay and analyzed by Michaelis-Menten kinetics. RESULTS: It is the first demonstration that RBP-8000 catalyzes the hydrolysis of acetylthiocholine (ATC). However, its catalytic efficiency (kcat/KM) against ATC is 1000-fold and 5000-fold lower than it against cocaine at 25 °C and 37 °C, respectively, suggesting RBP-8000 has the desired substrate selectivity for cocaine over ACh. CONCLUSION: Given the fact that clinically relevant dose of RBP-8000 displays insignificant cholinesterase activity relative to endogenous cholinesterases in human, administration of RBP-8000 is unlikely to produce any significant cholinergic side-effects. This study provides supplemental evidences in support of further development of RBP-8000 towards a clinically used pharmacotherapy for cocaine overdose.


Assuntos
Hidrolases de Éster Carboxílico/farmacocinética , Colinesterases/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína/metabolismo , Overdose de Drogas/tratamento farmacológico , Humanos , Hidrólise/efeitos dos fármacos , Inativação Metabólica/efeitos dos fármacos
13.
Mol Genet Metab ; 128(1-2): 75-83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31097363

RESUMO

The catabolism of ganglioside GM2 is dependent on the lysosomal enzyme ß-hexosaminidase A and a supporting lipid transfer protein, the GM2 activator protein. A genetically based disturbance of GM2 catabolism, leads to several subtypes of the GM2 gangliosidosis: Tay-Sachs disease, Sandhoff disease, the AB-variant and the B1-variant, all of them having GM2 as major lysosomal storage compound. Further on it is known that the gangliosides GM2 and GM3 accumulate as secondary storage compounds in mucopolysaccharidoses, especially in Hunter disease, Hurler disease, Sanfilippo disease and Sly syndrome, with chondroitin sulfate as primary storage compound. The exact mechanism of ganglioside accumulation in mucopolysaccaridoses is still a matter of debate. Here, we show that chondroitin sulfate strongly inhibits the catabolism of membrane-bound GM2 by ß-hexosaminidase A in presence of GM2 activator protein in vitro already at low micromolar concentrations. In contrast, hyaluronan, the major storage compound in mucopolysaccharidosis IX, a milder disease without secondary ganglioside accumulation, is a less effective inhibitor. On the other hand, hydrolysis of micellar-bound GM2 by ß-hexosaminidase A without the assistance of GM2AP was not impeded by chondroitin sulfate implicating that the inhibition of GM2 hydrolysis by chondroitin sulfate is most likely based on an interaction with GM2AP, the GM2AP-GM2 complex or the GM2-carrying membranes. We also studied the influence of some cationic amphiphilic drugs (desipramine, chlorpromazine, imipramine and chloroquine), provoking drug induced phospholipidosis and found that all of them inhibited the hydrolysis of GM2 massively.


Assuntos
Gangliosídeo G(M2)/antagonistas & inibidores , Gangliosídeo G(M2)/metabolismo , Mucopolissacaridoses/fisiopatologia , Tensoativos/farmacologia , Cátions/química , Sulfatos de Condroitina/farmacologia , Glicosaminoglicanos/farmacologia , Humanos , Hidrólise/efeitos dos fármacos
14.
Biotechnol Appl Biochem ; 66(4): 607-616, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31056790

RESUMO

Lipases are surface-active enzymes, acting on their substrates at the polar/nonpolar interface in emulsions. This study was aimed to test whether their activity, specificity, and the rates of formation/degradation of the various hydrolysis intermediates (i.e., mono- and diglycerides of interest as surface-active agents) could be modulated by adhesion of the triglyceride substrates as a thin layer on the surface of solids. These hypotheses were tested by using an array of food-grade lipases used in bakery, testing various types of starch as the "solid" phase. Starch-dependent increase in the hydrolysis rate was tested by pH-stat techniques on pure triglycerides and on food-grade oils in diluted emulsions. Starch-related improvements in the rate of fatty acids release were most evident at temperatures above 40 °C, and when using maize starch instead of wheat starch. Starch-dependent changes in the nature of the hydrolysis products were tested by chromatographic profiling of ethyl ether extracts from aqueous slurries containing up to 33% fat and 33% starch. Accumulation of mono- and diglycerides as hydrolysis intermediates was found to be modulated by the type of oil being used, by the reaction conditions, as well as by the enzyme nature and amount.


Assuntos
Lipase/metabolismo , Amido/metabolismo , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Hidrólise/efeitos dos fármacos , Cinética , Lipase/química , Amido/química , Amido/farmacologia , Especificidade por Substrato/efeitos dos fármacos , Triglicerídeos/química , Triglicerídeos/metabolismo
15.
Molecules ; 24(10)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117172

RESUMO

The aim of this study was to isolate and purify antioxidative peptides from Pacific herring (Clupea pallasii) protein. Five enzymes (pepsin, trypsin, papain, flavourzyme, and neutrase) were used for protein hydrolysis, and Pacific herring protein hydrolysates (PHPH) were separated by ultrafiltration. The fraction with the molecular weight below 3500 Da exhibited the highest in vitro antioxidant activities and cellular antioxidant activity. The PHPH was isolated and purified by consecutive chromatographic methods including gel filtration chromatography and reverse high-performance liquid chromatography (RP-HPLC). The purified antioxidant peptides were identified as Leu-His-Asp-Glu-Leu-Thr (MW = 726.35 Da) and Lys-Glu-Glu-Lys-Phe-Glu (MW = 808.40 Da), and the IC50 values of cellular antioxidant activity were 1.19 ± 0.05 mg/mL and 1.04 ± 0.06 mg/mL. The results demonstrate that is possible to produce natural antioxidative peptides from Pacific herring protein via enzymatic hydrolysis and purification.


Assuntos
Antioxidantes/química , Peixes/metabolismo , Fragmentos de Peptídeos/química , Peptídeos/química , Sequência de Aminoácidos , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Endopeptidases/farmacologia , Hidrólise/efeitos dos fármacos , Metaloendopeptidases/farmacologia , Papaína/farmacologia , Pepsina A/farmacologia , Fragmentos de Peptídeos/efeitos dos fármacos , Peptídeos/genética , Peptídeos/isolamento & purificação , Hidrolisados de Proteína/efeitos dos fármacos , Tripsina/farmacologia
16.
Nat Chem Biol ; 15(6): 556-559, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086327

RESUMO

Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and specific small-molecule inhibitor of the NLRP3 pathway, but its molecular target is not defined. Here, we show that MCC950 directly interacts with the Walker B motif within the NLRP3 NACHT domain, thereby blocking ATP hydrolysis and inhibiting NLRP3 activation and inflammasome formation.


Assuntos
Trifosfato de Adenosina/antagonistas & inibidores , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Sulfonas/farmacologia , Trifosfato de Adenosina/metabolismo , Sítios de Ligação/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/química , Humanos , Hidrólise/efeitos dos fármacos , Inflamassomos/biossíntese , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfonas/química
17.
Carbohydr Polym ; 217: 126-134, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31079668

RESUMO

Longan pulp is an excellent source of polysaccharides and other nutrients that have many health benefits. However, longans is susceptible to pulp breakdown after harvest and loses its nutrition values. To solve this problem, this study aimed to study the effects of a novel chitosan, Kadozan, on pulp breakdown index, contents of pectin, cellulose and hemicelluloses, and activities of enzymes in longan pulp relating to disassembly of polysaccharides (XET, PE, PG, ß-Gal, and cellulase). The data illustrated that, compared to the control longans, chitosan-treated longans contained higher amounts of CWM, CSP, ISP, cellulose and hemicelluloses, but exhibited lower pulp breakdown index, lower activities of cell wall-disassembling enzymes, and contained lower WSP amount. These results suggested that Kadozan with a dilution of 1:500 (VKadozan: VKadozan + Water) could significantly decrease activities of disassembling-enzymes and depolymerization of polysaccharides in cell wall, and subsequently alleviate pulp breakdown and prolong storage-life of postharvest longans.


Assuntos
Parede Celular/efeitos dos fármacos , Quitosana/farmacologia , Inibidores Enzimáticos/farmacologia , Frutas/metabolismo , Polissacarídeos/metabolismo , Sapindaceae/metabolismo , Parede Celular/metabolismo , Celulose/metabolismo , Conservação de Alimentos/métodos , Qualidade dos Alimentos , Glicosídeo Hidrolases/antagonistas & inibidores , Hidrólise/efeitos dos fármacos , Pectinas/metabolismo
18.
Molecules ; 24(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052602

RESUMO

In this study, effects of different pretreatment methods on the enzymatic digestibility of Pennisetum alopecuroides, a ubiquitous wild grass in China, were investigated to evaluate its potential as a feedstock for biofuel production. The stalk samples were separately pretreated with H2SO4, NaOH and FeCl3 solutions of different concentrations at 120 °C for 30 min, after which enzymatic hydrolysis was conducted to measure the digestibility of pretreated samples. Results demonstrated that different pretreatments were effective at removing hemicellulose, among which ferric chloride pretreatment (FCP) gave the highest soluble sugar recovery (200.2 mg/g raw stalk) from the pretreatment stage. In comparison with FCP and dilute acid pretreatment (DAP), dilute alkaline pretreatment (DALP) induced much higher delignification and stronger morphological changes of the biomass, making it more accessible to hydrolysis enzymes. As a result, DALP using 1.2% NaOH showed the highest total soluble sugar yield through the whole process from pretreatment to enzymatic hydrolysis (508.5 mg/g raw stalk). The present work indicates that DALP and FCP have the potential to enhance the effective bioconversion of lignocellulosic biomass like P. alopecuroides, hence making this material a valuable and promising energy plant.


Assuntos
Ácidos/farmacologia , Antiácidos/farmacologia , Cloretos/farmacologia , Enzimas/metabolismo , Compostos Férricos/farmacologia , Pennisetum/efeitos dos fármacos , Pennisetum/metabolismo , Biomassa , Fermentação , Hidrólise/efeitos dos fármacos , Açúcares/metabolismo
19.
Int J Biol Macromol ; 133: 420-427, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31026522

RESUMO

Type-2 diabetes mellitus and its related complications including dyslipidemia and oxidative stress have been threating the health of a large number of patients all over the world. In this study, FCPC, one polysaccharide fraction separated from the polysaccharides of Chinese medicine Fructus Corni (FCPs), revealed obvious inhibitory effects against α-amylase and α-glucosidase, and marked insulin-sensitizing effect by increasing insulin secretion and promoting pancreatic ß cell proliferation. In addition, in streptozotocin (STZ)-induced diabetic rats, the polysaccharide fraction not only significantly restrained the increase of food (p < 0.05) and water (p < 0.01) intake at 800 mg/kg, but also significantly controlled the increase of levels for sugar (p < 0.01), insulin (p < 0.05) and HOMA-IR value (p < 0.05) in blood at 800 mg/kg on 42th day. Meanwhile, the reduced glycogen contents in liver (p < 0.01) and skeletal (p < 0.01) muscle caused by STZ were prominently improved, while the dyslipidemia status and oxidative damage were markedly ameliorated. Therefore, FCPC could be developed to natural medicines and functional foods in the treatment of diabetes and its complications including dyslipidemia status and oxidative stress.


Assuntos
Antioxidantes/farmacologia , Cornus/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Polissacarídeos/farmacologia , Animais , Antioxidantes/uso terapêutico , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Metabolismo dos Carboidratos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Ingestão de Líquidos/efeitos dos fármacos , Glicogênio/metabolismo , Hidrólise/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculos/efeitos dos fármacos , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Ratos , Ratos Sprague-Dawley
20.
ACS Appl Mater Interfaces ; 11(19): 18013-18023, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31010291

RESUMO

Biodegradable electronic devices that physically disappear in physiological or environmental solutions are of critical importance for widespread applications in healthcare management and environmental sustainability. The precise modulation of materials and devices dissolution with on-demand operational lifetime, however, remain a key challenge. Silicon nanomembranes (Si NMs) are one of the essential semiconductor components for high-performance biodegradable electronics at the system level. In this work, we discover unusual hydrolysis behaviors of Si NMs that are significantly dependent on the dimensions of devices as well as their surface chemistry statuses. The experiments show a pronounced increase in hydrolysis rates of p-type Si NMs with larger sizes, and mechanical stirring introduces a significant decrease in dissolution rates. The presence of phosphates and potassium ions in solutions, or lower dopant levels of Si NMs will facilitate the degradation of Si NMs and will also lead to a stronger size-dependent effect. Molecular dynamics simulations are performed to reveal ion adsorption mechanisms of Si NMs under different surface charge statuses and confirm our experimental observations. Through geometrical designs, Si NM-based electrode arrays with tunable dissolution lifetime are formed, and their electrochemical properties are analyzed in vitro. These results offer new controlling strategies to modulate the operational time frames of Si NMs through geometrical design and surface chemistry modification and provide crucial fundamental understandings for engineering high-performance biodegradable electronics.


Assuntos
Membranas Artificiais , Nanoestruturas/química , Silício/química , Cristalização , Eletrônica , Hidrólise/efeitos dos fármacos , Íons/química , Semicondutores
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