Relevant bibliographies by topics / Enzyme inhibition

Academic literature on the topic 'Enzyme inhibition'

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Published: 4 June 2021
Last updated: 31 August 2024

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Journal articles on the topic "Enzyme inhibition"

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Minchenko, O. H. "Inhibition of ERN1 signaling enzyme affects hypoxic regulation." Ukrainian Biochemical Journal 87, no. 2 (April 27, 2015): 76–87. http://dx.doi.org/10.15407/ubj87.02.076.

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Ismail, Muhammad, Javid Hussain, Arif-ullah Khan, Abdul Latif Khan, Liaqat Ali, Farman-ullah Khan, Amir Zada Khan, Uzma Niaz, and In-Jung Lee. "Antibacterial, Antifungal, Cytotoxic, Phytotoxic, Insecticidal, and Enzyme Inhibitory Activities ofGeranium wallichianum." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/305906.

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The present study describes the phytochemical investigations of the crude extracts of rhizomes and leaves ofGeranium wallichianum. The crude extracts were fractionated to obtainn-hexane, ethyl acetate, andn-butanol fractions, which were subjected to different biological activities and enzyme inhibition assays to explore the therapeutic potential of this medicinally important herb. The results indicated that the crude extracts and different fractions of rhizomes and leaves showed varied degree of antimicrobial activities and enzyme inhibitions in different assays. Overall, the rhizome extract and its different fractions showed comparatively better activities in various assays. Furthermore, the purified constituents from the repeated chromatographic separations were also subjected to enzyme inhibition studies against three different enzymes. The results of these studies showed that lipoxygenase enzyme was significantly inhibited as compared to urease. In case of chemical constituents, the sterols (2–4) showed no inhibition, while ursolic acid (1) and benzoic ester (6) showed significant inhibition of urease enzymes.
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Ochs, Raymond S. "Understanding Enzyme Inhibition." Journal of Chemical Education 77, no. 11 (November 2000): 1453. http://dx.doi.org/10.1021/ed077p1453.

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Ault, Addison. "Understanding Enzyme Inhibition." Journal of Chemical Education 79, no. 3 (March 2002): 311. http://dx.doi.org/10.1021/ed079p311.1.

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Ochs, Raymond S. "Understanding Enzyme Inhibition." Journal of Chemical Education 79, no. 3 (March 2002): 311. http://dx.doi.org/10.1021/ed079p311.2.

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Wirasti, Wirasti, Titi Lestari, and Isyti'aroh Isyti'aroh. "Penghambatan Ekstrak Daun Kremah (Alternanthera sessilis) Terhadap Enzim α-amilase secara In-Vitro." Pharmacon: Jurnal Farmasi Indonesia 18, no. 1 (June 30, 2021): 68–74. http://dx.doi.org/10.23917/pharmacon.v18i01.14657.

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An important treatment for type 2 diabetes is controlling blood glucose levels. α-amylase enzyme in the body plays a role in breaking down carbohydrates into starch. Control of the amylase enzyme is needed in diabetes cases Kremah plant (Alternanthera sessillis) is a plant whose leaves can be used to lower blood glucose levels because it contains secondary metabolites, one of which is flavonoids which can inhibit the α-amylase enzyme. The purpose of this study was to determine the activity and inhibition value of kremah leaves against the α-amylase enzyme. The method used in this research is the enzymatic reaction by measuring the intensity of the color using UV-Vis spectrophotometry. The IC50 value obtained by α-amylase enzyme inhibition was 101.89±7,21 μg / ml while the IC50 acarbose value was 127.17±4,42 μg / ml. These results indicate that kremah leaf extract has activity (hyperglycemia) by inhibiting complex carbohydrate hydrolyzing enzymes such as the α-inhibition enzyme α-Amylase which is good compared to acarbose because the IC50 value of the extract is smaller, so that the leaves of kremah has inhibiting of the α-amylase enzyme.
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Rousdy, Diah Wulandari, and Elvi Rusmiyanto Wardoyo. "In Vitro Antiinflammatory Activity of Bajakah (Spatholobus littoralis) Stem Extract." Biosaintifika: Journal of Biology & Biology Education 15, no. 2 (August 16, 2023): 150–57. http://dx.doi.org/10.15294/biosaintifika.v15i2.36227.

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The plant of Bajakah tampala (Spatholobus littoralis Hassk) has been utilized in traditional medication. Previous studies have proven the existence of in vivo anti-inflammatory activities of Bajakah plant (S. littoralis) in lowering the degree of carrageenan-induced paw oedema in mice. This study aims to determine the anti-inflammatory mechanism of S. littoralis extract in vitro through an approach of enzyme inhibition involved in the inflammatory reaction. The concentration of ethanol extract of Bajakah used was 0.1; 0.2; 0.4; 0.8; 1.6 mg/ml. The parameters measured were lipoxygenase enzyme inhibition, protein denaturation inhibition, protease enzyme inhibition, as well as plasma membrane stabilization. The results of the study showed the potential of the ethanol extract of Bajakah stems in inhibiting the inflammatory process viewed from the ability to inhibit inflammation-related enzymes. S. littoralis extract concentration of 1.6 mg/ml showed the best inhibition of the protein denaturation process (75.9%), the inhibition of trypsin protease enzyme (26.1%) and the stability of erythrocyte membrane (93.7%). However, the extracts of S. littoralis did not provide inhibition for the lipoxygenase enzyme in the range of 0.2-3.8%. This study proves the role of S. littoralis extract in the anti-inflammatory mechanism. It has the potential to be developed into standardized herbs.
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Masson, Patrick, and Aliya R. Mukhametgalieva. "Partial Reversible Inhibition of Enzymes and Its Metabolic and Pharmaco-Toxicological Implications." International Journal of Molecular Sciences 24, no. 16 (August 19, 2023): 12973. http://dx.doi.org/10.3390/ijms241612973.

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Partial reversible inhibition of enzymes, also called hyperbolic inhibition, is an uncommon mechanism of reversible inhibition, resulting from a productive enzyme–inhibitor complex. This type of inhibition can involve competitive, mixed, non-competitive and uncompetitive inhibitors. While full reversible inhibitors show linear plots for reciprocal enzyme initial velocity versus inhibitor concentration, partial inhibitors produce hyperbolic plots. Similarly, dose–response curves show residual fractional activity of enzymes at high doses. This article reviews the theory and methods of analysis and discusses the significance of this type of reversible enzyme inhibition in metabolic processes, and its implications in pharmacology and toxicology.
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AFFI, Sopi Thomas, Doh SORO, Souleymane COULIBALY, Bibata KONATE, and Nahossé ZIAO. "Modeling anticancer pharmacophore based on inhibition of HDAC7." SDRP Journal of Computational Chemistry & Molecular Modeling 5, no. 3 (2021): 657–63. http://dx.doi.org/10.25177/jccmm.5.3.ra.10776.

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Histone deacetylases (HDACs) are the target inhibition enzymes in cancer treatment via chemotherapy. Application of this therapeutic technique requires the use of drugs whose side effects are reduced and tiny with necessary safety. In this study, the methods and tools of pharmacophore modeling were used to investigate ten molecules known for their anticancer properties. Particular attention has been given to pinpoint a promising anti-cancer pharmacophore in order to lead new effective inhibitors. Using Discovery Studio 2.5 software, the ten compounds were docked within the active site of the HDAC7 enzyme. Analysis of the binding characteristics of all the compounds collected and tested in the model resulted in the characteristics produced by the 3D pharmacophore of the selected hypothesis. This led to note that the efficiency of any HDAC enzyme inhibitor was related to the characteristics of the designed pharmacophore. At the end, the pharmacophore hypothesis used here was presented as a useful basis for the development of anticancer compounds. Keywords: Pharmacophore, 3c0z, HDAC7, QSAR
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S, Iyswarya, Visweswaran S, Muthukumar N J, Tamilselvi S, and Mathukumar S. "Revealing Anti-diabetic potential of Siddha formulation Gandhaka Sarkkarai using alpha amylase and alpha glucosidase enzyme inhibition assay." International Journal of Ayurvedic Medicine 13, no. 2 (July 8, 2022): 515–19. http://dx.doi.org/10.47552/ijam.v13i2.2552.

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Background: Diabetes mellitus (DM) is a complex metabolic disorder which involves multiple pathology manifested with increased blood glucose, neural degeneration, chronic inflammation, organ dysfunction etc. Hyperactive metabolic enzymes like alpha amylase and alpha glucosidase that are involved in digestion of starch and sucrose further upswings the postprandial hyperglycaemia by rushing excess glucose moieties into the bloodstream. Drugs that effectively inhibit the action of these digestive enzymes may be expected to better regulate the post prandial blood glucose in the diabetic patients. Conventional anti-diabetic agents offer potential side effects upon long-term usage which includes vomiting, diarrhoea, pigmentation, GI disturbance, dark urination etc.The Siddha system of medicine has excelled in the art of treating human ailments for several centuries. Aim: Present investigation designed to investigate the anti-diabetic potential of siddha formulation Gandhaka sarkkarai (GS) using in-vitro alpha amylase and alpha glucosidase enzyme inhibition assay model. Results: It was evidenced from the outcome of the in-vitro data’s that the siddha formulation GS shown significant inhibition against alpha glucosidase enzyme with the maximum inhibition of about 50.44 % and the corresponding IC50 is 471.1 μg/ml, similar pattern of activity were observed against alpha amylase enzyme with the inhibition of 60.84 % (IC50 400.9 μg/ml). Conclusion: Our data concludes that siddha formulation GS possess significant anti-diabetic activity via inhibiting two major carbohydrate-digesting enzymes, further studies needs to extrapolated at pre-clinical level in order to ascertain the efficacy of the formulation. Key words: Diabetes mellitus, Alpha amylase, Alpha glucosidase, Siddha, Gandhaka sarkkarai, Enzyme inhibition assay, In-vitro, Anti-diabetic activity.
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Dissertations / Theses on the topic "Enzyme inhibition"

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Edge, Colin Michael. "Theoretical studies of enzyme inhibition." Thesis, University of St Andrews, 1989. http://hdl.handle.net/10023/14388.

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The glyoxalase enzyme system catalyses the conversion of methylglyoxal to D-lactic acid. The first of the two component enzymes, glyoxalase I, is responsible for the transfer of two protons in an iscmerisation reaction. This enzyme has been ascribed a role in tumorigenesis in the past and some of its inhibitors are known to be carcinostatic. This thesis describes quantum chemical calculations on the enzyme mechanism and on some enzyme inhibitors. The calculations on the mechanism of the enzyme take the form of studies of model reaction schemes, with minimal and split-valence basis sets. The calculation of the energies of various intermediates has led to the evaluation of different pathways as models of the enzyme mechanism. The comparison of different substituted compounds has led to further conclusions on the part played by the sulphur atom in the enzyme-catalysed reaction. Two main groups of inhibitor molecules are discussed; these are flavone and coumarin derivatives. The molecular electrostatic potential of these molecules has been calculated on various surfaces, using a minimal basis set, to attempt to correlate this property with the compounds' inhibitory power. A FORTRAN program is presented which depicts calculated properties on the surfaces. This program allowed the identification of various regions which seemed to be indicative of the inhibitory strength of the compounds.
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Kakkar, Tarundeep Singh. "Theoretical studies on enzyme inhibition kinetics." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/289017.

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Enzyme inhibition studies are conducted to characterize enzymes and to examine drug-drug interactions. To characterize the inhibitory process (competitive, non-competitive and uncompetitive) and to determine the inhibitory constant (Kᵢ), data analysis techniques (e.g., Dixon, Lineweaver-Burk, etc.) are used to linearize the inherently non-linear rate of substrate metabolism vs. substrate concentration data. These techniques were developed before the general use of computers. However, many investigators still rely on these techniques in spite of the easy availability of non-linear regression fitting programs. In Chapter 2, three methods (simultaneous nonlinear regression fit (SNLR); Dixon; non-simultaneous, nonlinear fit [K(m,app)]) were compared for estimating Ki from simulated data sets generated from a competitive inhibition model equation with 10% CV added random error to the data values. Of the three methods, the SNLR method was found to be the most robust, the fastest and easiest to implement. The K(m,app) method also gave good estimates but was more time-consuming. The Dixon method failed to give accurate and precise estimates of Kᵢ. The purpose of the study in Chapter 3 was to examine the minimal experimental design needed to obtain reliable and robust estimates of Kᵢ (as well as V(max) and K(m)). Four cases were examined. In the experimental design that relied upon the least amount of data, a control data set was fit simultaneously with one of the substrate-inhibitor pairs (25-10 or 250-100 μM). A total of 4 rate values were analyzed per fit (i.e., 3 control + 1 inhibitor value). A total of 100 data sets were fit per substrate-inhibitor pair. The preceding was repeated for a random error of 20 %CV. Thus, the total number of experiments was reduced from 108 (in Chapter 2) to 12 (in Chapter 3) (Case IV). Good estimates of the enzyme kinetic parameters were obtained. In Chapter 4, the ability of the SNLR method to identify the correct mechanism of inhibition was evaluated; competitive or noncompetitive enzyme-inhibition. Two experimental designs were examined ("conventional, non-optimal" and "semi-minimal"). The semi-minimal design was successful in discriminating between the two enzyme-inhibition mechanisms even for data with 30 %CV added random error.
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Bjelic, Sinisa. "Molecular Simulation of Enzyme Catalysis and Inhibition." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7468.

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Axamawaty, Mohammed Taleb Hassan. "Inhibition and inactivation of hydrolases." Thesis, University of Bristol, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.481028.

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Khan, Amjad. "NMR spectroscopy studies of enzyme function and inhibition." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:698d69c7-d4f1-4bc7-bf0b-3b9e7fb3a4fe.

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The work described in this Thesis focuses on the application of NMR spectroscopy methods in understanding the function and inhibition of two protein systems; these are ?-butyrobetaine hydroxylase (BBOX) and the bacterial potassium ion efflux (Kef) system. BBOX belongs to the super family of enzymes called the 2- oxoglutarate (2OG) and FeII dependent oxygenase and is involved in the biosynthesis of L-carnitine in humans and other prokaryotes. BBOX is a current drug target for the treatment of myocardial infarction. Kef is a ligandgated system that protects bacteria from toxic electrophilic species. Kef is inhibited by the binding of cytoplasmic glutathione (GSH) to KTN (K+ transport and nucleotide) binding domains and activated by glutathione-S-conjugates (GS-X). Since bacterial Kef activation during electrophilic exposure is a critical determinant of their survival, perturbation of Kef activity is potentially a novel target for the development of antibiotic drugs. 1H NMR direct ligand-observation was employed to study the binding interaction of the natural substrate ?- butyrobetaine (GBB) and co-substrate 2OG with BBOX. A 1H NMR-based dual-reporter ligand displacement method was developed to assess the nature of inhibitor binding to BBOX i.e to determine whether an inhibitor competes with GBB or 2OG or both. The method was exemplified with a set of isoquinoline-based inhibitors; the results reveal 'cystallographically unexpected' structure-activity relationship with some inhibitors competing 2OG only and some competing both 2OG and GBB. Using 1H NMR spectroscopy, a simple and efficient BBOX inhibition assay was developed for inhibitor IC50 measurement. Similarly, 1H NMR-based assays were applied to demonstrate that the cation-p interaction between the substrates and aromatic cage residues of BBOX play a critical role in BBOX substrate recognition. 1H NMR spectroscopy was applied to show that in the absence of a 2OG oxygenase, ascorbate in the assay mixture is slowly degraded by the dissolved oxygen to yield H2O2 which simultaneously leads to 2OG breakdown into succinate. It is proposed that in the assays of 2OG oxygenases, the apparent increase in the level of "uncoupled" 2OG turnover with ascorbate over time could possibly be due to the artifacts of the ascorbate induced-2OG breakdown instead of being due to enzyme catalysis. Other reducing agents were also found to oxidise identically by the dissolved oxygen as ascorbate in the mixture and result in 2OG breakdown. In the Kef system, 1H NMR direct ligand-observation was applied to investigate the influence of each functional group of the Kef activating ligand glutathione-S-N-tertiary butylsuccinimide on its binding interaction (KD 0.4 μM) with Kef-QCTD (Q-linker carboxy terminal domain; a KTN domain) from Shewanella denitrificans (sd) with the aim of developing novel non-peptidic ligands (antibacterial agents) of Kef. In addition, 19F NMR was employed to develop an efficient ligand-observed binding assay for Kef that was used for ligand screening as well as measuring their binding dissociation constant value from a single NMR spectrum. Finally, a 1H NMR technique was applied to confirm that the electron density found in the nucleotide binding pocket in the crystal structure of apo-sdKef-QCTD is unambiguously an AMP molecule that is naturally bound to the protein and has a role in stabilising the dimeric form of KTN domains (Kef proteins).
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Ghous, T. "Flow injection determination of drugs by enzyme inhibition." Thesis, University of Hull, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296138.

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Apperley, Kim Yang-Ping. "Reversible and Photolabile Inhibitors for Human Tissue Transglutaminase." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36593.

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Tissue transglutaminase (TG2) is a calcium-dependent enzyme that natively catalyses the formation of isopeptidic bonds between protein- or peptide-bound glutamine and lysine residues. Physiologically, it is ubiquitously expressed in tissues, with roles in cellular differentiation, extracellular matrix stabilisation, and apoptosis, among others. However, its unregulated activity has been associated with various pathologies including fibrosis, cancer and celiac disease. Since most pathologies are associated with an increased transamidation activity, efforts have been directed towards the development of TG2 inhibitors. In this context, the work described in this thesis is centred on reversible inhibitors, building on recent work done within the Keillor group in two directions, namely localisation and potency. In a localisation-driven approach, we developed a photolabile derivative of a known reversible inhibitor, in order to form a covalent bond with the enzyme and determine the inhibitor’s binding site. In tandem, we optimised a protocol for the expression of TG2 incorporating ArgΔ10 and LysΔ8, amino acids that are 13C- and 15N-labelled to provide a mass shift of 10 and 8 Da, respectively, compared to the corresponding unlabelled amino acids. This “heavy” TG2 was developed as a tool for reference in the analysis of the tryptic digest of labelled protein. In a potency-driven approach, based on the observation that previous trans cinnamoyl inhibitor scaffolds were susceptible to nucleophilic attack by glutathione, we developed a bis(triazole) scaffold with reduced electrophilicity. The preparation of a small library of compounds showed that this scaffold demonstrates a preference for electron-withdrawing substituents, such as nitro groups. Continuing in a potency-driven approach, and inspired by work done in the identification of glutathione-resistant scaffolds, we studied a new alkynyl scaffold. While still susceptible to glutathione addition, these compounds showed a marked improvement in potency, with the lead compound having an IC50 of 930 nM and being established as a competitive inhibitor with a Ki of 420 nM, our most potent reversible inhibitor to date. Furthermore, this scaffold also produced an inhibitor lacking nitro groups (to limit eventual cellular toxicity), but maintaining good potency, with an IC50 value of 3.03 μM.
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Kownarumit, Supaporn. "Multiplex screening using enzyme inhibition, fluorescence detection and chemometrics." Thesis, Loughborough University, 2006. https://dspace.lboro.ac.uk/2134/12308.

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Fluorescence enzyme inhibition assays have been established for a number of years as valuable methods of analysis in clinical chemistry and other fields. Those in common use are normally single analyte assays. However, in many cases (e.g. drug screening) dual or multiplex assays would be much more valuable, with the advantages of increased information content, saving in time and costs, and the elimination of some sources of sampling variance. This project has investigated single and dual screening assays of enzyme inhibitors, namely 3-nitrophenylboronic acid (3-NPBA), phenylethyl /3-0- thiogalactopyranoside (PETG) and sodium vanadate (VI), using flow injection fluorescence spectroscopy and chemometric methods to resolve strongly overlapping fluorescence spectra. The single and dual screening assays have been based on flow injection analysis methodology, with immobilised enzymes on solid phase reactors to investigate the enzyme inhibitors. The assays were rapid, allowing around 15-25 measurements to be made per hour. The inhibitions of alkaline protease, alkaline phosphatase and /3-galactosidase with their inhibitors at flg/ml levels were achieved. An alternative approach to these dual assays has been investigated by the use of multivariate techniques. Such techniques allow accurate and reliable results to be obtained even from spectra that contain extremely overlapping signals. Moreover, preliminary investigation of three fluorophores which gave strongly overlapping spectra, using flow injection fluorescence spectroscopy and partial least squares (PLS-1) model has been successful. By combination of this flow injection fluorescence spectroscopy with the use of chemometrics, many applications can be envisaged in biochemical, clinical, and pharmaceutical industries. With the findings of this research the system described here can be developed for use in high throughput screening of candidate drug molecules and many screening processes throughout the different industries.
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Page, Simon Matthew. "Ruthenium anticancer complexes : a targeted approach to enzyme inhibition." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608027.

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Al-Timari, A. A. A. K. "Binding determinants for some glutathione-dependent enzymes." Thesis, University of Essex, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354003.

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Books on the topic "Enzyme inhibition"

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Graham, MacGregor, Sever Peter S, International Symposium on ACE Inhibition (1st : 1989 : London, England), and International Symposium on ACE Inhibition (2nd : 1991 : London, England), eds. Current advances in ACE inhibition. Edinburgh: Churchill Livingstone, 1989.

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Lu, Chuang, and Albert P. Li, eds. Enzyme Inhibition in Drug Discovery and Development. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2009. http://dx.doi.org/10.1002/9780470538951.

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1930-, Smith H. J., and Simons Claire, eds. Enzymes and their inhibition: Drug development. Boca Raton: CRC Press, 2005.

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F, Cleland John G., ed. The Clinician's guide to ACE inhibition. Edinburgh: Churchill Livingstone, 1993.

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(Australia), Materials Research Laboratories, ed. Inhibition of EEL acetylcholinesterase by nerve agents: A stopped-flow study. Ascot Vale, Vic: Dept. of Defence, Materials Research Laboratories, 1985.

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1932-, Sonnenblick Edmund H., Laragh John H. 1924-, and Lesch Michael, eds. New frontiers in cardiovascular therapy: Focus on angiotensin converting enzyme inhibition. Princeton: Excerpta Medica, 1989.

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Ahlström, Marie. Cytochrome P450, metabolism and inhibition: Computational and experimental studies. Göteborg: Göteborg University, 2007.

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Chuang, Lu, and Li A. P, eds. Enzyme inhibition in drug discovery and development: The good and the bad. Hoboken, N.J: John Wiley, 2009.

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M, Dowsett, ed. Aromatase inhibition: Then, now, and tomorrow. London: Parthenon Pub. Group, 1994.

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A, MacGregor G., and Sever Peter S, eds. Current advances in ACE inhibition 2: Proceedings of an Internationalsymposium, Queen Elizabeth II Conference Centre, London, UK 17-21 February 1991. Edinburgh: Churchill Livingstone, 1991.

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Book chapters on the topic "Enzyme inhibition"

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Ellenbroek, Bart, Alfonso Abizaid, Shimon Amir, Martina de Zwaan, Sarah Parylak, Pietro Cottone, Eric P. Zorrilla, et al. "Enzyme Inhibition." In Encyclopedia of Psychopharmacology, 486. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1193.

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Lasseter, Benjamin F. "Enzyme Inhibition." In Biochemistry in the Lab, 127–36. Names: Lasseter, Benjamin F., author. Title: Biochemistry in the lab : a manual for undergraduates / by Benjamin F. Lasseter. Description: Boca Raton, Florida : CRC Press, [2020]: CRC Press, 2019. http://dx.doi.org/10.1201/9780429491269-13.

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Punekar, N. S. "Enzyme Inhibition Analyses." In ENZYMES: Catalysis, Kinetics and Mechanisms, 231–36. Singapore: Springer Singapore, 2018. http://dx.doi.org/10.1007/978-981-13-0785-0_20.

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Baici, Antonio. "Slow-Onset Enzyme Inhibition." In Kinetics of Enzyme-Modifier Interactions, 367–444. Vienna: Springer Vienna, 2015. http://dx.doi.org/10.1007/978-3-7091-1402-5_8.

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Mehdi, Shujaath. "COVALENT ENZYME INHIBITION IN DRUG DISCOVERY AND DEVELOPMENT." In Enzyme Technologies, 81–129. Hoboken, NJ: John Wiley & Sons, Inc, 2013. http://dx.doi.org/10.1002/9781118739907.ch3.

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Tallarida, Ronald J., and Rodney B. Murray. "Enzyme Kinetics II: Competitive Inhibition." In Manual of Pharmacologic Calculations, 63–66. New York, NY: Springer New York, 1987. http://dx.doi.org/10.1007/978-1-4612-4974-0_20.

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Tallarida, Ronald J., and Rodney B. Murray. "Enzyme Kinetics III: Noncompetitive Inhibition." In Manual of Pharmacologic Calculations, 66–69. New York, NY: Springer New York, 1987. http://dx.doi.org/10.1007/978-1-4612-4974-0_21.

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Dudda, Angela, and Gert Ulrich Kürzel. "Drug–Drug Interaction – Enzyme Inhibition." In Drug Discovery and Evaluation, 551–57. Berlin, Heidelberg: Springer Berlin Heidelberg, 2006. http://dx.doi.org/10.1007/3-540-29804-5_28.

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Arduini, Fabiana, and Aziz Amine. "Biosensors Based on Enzyme Inhibition." In Advances in Biochemical Engineering/Biotechnology, 299–326. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/10_2013_224.

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Dudda, Angela, and Gert Ulrich Kuerzel. "Drug–Drug Interaction: Enzyme Inhibition." In Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays, 989–1004. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-25240-2_44.

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Conference papers on the topic "Enzyme inhibition"

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Visser, A., and D. G. Meuleman. "IRREVERSIBLE INHIBITION OF THE THROMBIN-MEDIATED SIGNAL TRANSFER." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644808.

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The inhibition of the thrombin-mediated signal transfer by a common irreversible inhibitor Z of the factor Xa complex (Xc a) and thrombin has been analysed for the two-step process of the Xc a-triggered formation of thrombin andthe consecutive splitting ok a thrombin-specific substrate S. Assuming that both proteolytic processes follow simple Michaelis—Menten kinetics, that the inhibition reactions are second-order and that the prothrombin and irreversible inhibitor are in excess it can be shown that:1. clotting time (tc) is inversely proportional to the time-averaged thrombin concentration2. the endpoint of the conversion of the thrombin specific substrate S reached at exhaustion of thrombin and the Xc a is inversely proportional to the square of the inhibitor concentration3. the continously monitored thrombin generation inhibition is a more sensitive assay than the classical two-stage thrombin generation inhibition assay4. the shift in the effective concentration range of the continuously monitored thrombin generation inhibition assay relative to the continuously monitored anti-Xa assay and to that of the continuously monitored anti-IIa assay, depends on the initial rate of formation of thrombin with the thrombin generation inhibition assay and the original enzyme concentrations of the anti-enzyme assays.It can further be shown that the above conclusions still hold when the Z-mediated (with Z = anti thrombin III e.g.) inhibitions are potentiated by heparin(oid)s.
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Cao, Yuqing, and Zhixuan Li. "Enzyme inhibition-based electrochemical biosensors for pesticide residues detection." In Third International Conference on Optoelectronic Science and Materials (ICOSM 2021), edited by Siting Chen and Pei Wang. SPIE, 2021. http://dx.doi.org/10.1117/12.2617693.

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Zhuravlev, A. M., V. V. Aksenov, V. N. Gavrilyuk, A. B. Golovanov, and I. V. Ivanov. "ALLOSTERIC INHIBITORS OF ALOX15 BASED ON LIGANDS PROVIDING MULTIDIRECTIONAL REGULATION OF LINOLEIC AND ARACHIDONIC ACIDS." In X Международная конференция молодых ученых: биоинформатиков, биотехнологов, биофизиков, вирусологов и молекулярных биологов — 2023. Novosibirsk State University, 2023. http://dx.doi.org/10.25205/978-5-4437-1526-1-76.

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Mammalian 15-lipoxygenases (ALOX15) are enzymes of lipid peroxidation. The pathophysiological role of ALOX15 metabolites, linoleic acid and arachidonic acid derivatives, has made this enzyme a target for pharmacological studies. Several indole and benzimidazole derivatives inhibit the activity of ALOX15 in a substrate-specific manner, but the molecular basis of this allosteric inhibition remains unclear.
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Enouf, J., R. Breadux, N. Bourdeau, and S. Levy-Toledano. "EVIDENCE FOR TWO DIFFERENT Ca2+TRANSPORT SYSTEMS ASSOCIATED WITH PLASMA AND INTRACELLULAR HUMAN PLATELET MEMBRANES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644490.

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The regulation of Ca2+ concentration in different cells involves two Ca2+ pumps. The presence of such mechanisms in human platelets is still controverted. We then investigated this question by using plasma and intracellular membranes obtained after simultaneous isolation by centrifugation ca 40% sucrose from a mixed 100,000 g membrane fraction.The Ca2+ uptake by the different membrane vesicles has been studied. Both membrane fractions took up Ca2+ and the Ca2+ transport systems exhibited a high affinity towards Ca 2+.However, the two associated Ca2+ transport systems showed a different time course and exhibited different oxalate sensitivity. The plasma membranes are not permeable to potassium oxalate, while the Ca2+ uptake was stimulated by potassium oxalate in intracellular membranes.Two Ca2+ activated ATPase activities are associated with the isolated membrane fractions and appeared different for the following parameters : 1) a different time course of the two enzyme activities; 2)a similar apparent affinity towards Ca2+ (10−7 M), though inhibition of the Ca2+ ATPase activity was only observed in intracellular membranes at 10−6 M Ca2+ ; 3)a different pH dependence with a maximum at pH 7 for the enzyme of intracellular membranes and pH 8 for the enzyme of plasma membranes; 4)a 10 fold difference in the ATP requirement of the enzymes, thus the maximal response was obtained with 20 uM for the intracellular membrane enzyme and with 200 uM for the plasma membrane enzyme ; 5) a different affinity for various nucleotides as energy donors with a higher specificity of the plasma membrane enzyme towards ATP ; 6) a different vanadate inhibition-dose reponse which did not exceed 60% for the plasma enzyme while it reached 100% for the intracellular enzyme.Taken together, these studies agree with the possible role of both a plasma membrane and a dense tubular system Ca2+ -ATPases in the regulation of Ca2+ concentration in human platelets.
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Campanella, L., R. Cocco, G. Favero, M. P. Sammartino, and M. Tomassetti. "INHIBITION ENZYME SENSOR FOR NICOTINE, NICOTINAMIDE AND NICOTINIC ACID DETERMINATION." In Proceedings of the 5th Italian Conference — Extended to Mediterranean Countries. WORLD SCIENTIFIC, 2000. http://dx.doi.org/10.1142/9789812792013_0005.

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Baba, Waqas, and Sajid Maqsood. "Novel antihypertensive and anticholesterolemic peptides from peptic hydrolysates of camel whey proteins." In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/qecs2081.

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Hypercholesterolemia and hypertension are major growing concerns that are managed by drugs that inhibit various metabolic enzymes. Milk hydrolysates have been reported to contain various bioactive peptides (BAP) that can inhibit various metabolic enzymes for enhancing human health. As such camel whey proteins were subjected to peptic hydrolysis using a full factorial model (33) with hydrolysis time, temperature, and enzyme concentration as factors. The resulting hydrolysates were analyzed for anti-hypercholesterolemic and hypertensive properties by studying the in vitro inhibition of various enzymatic markers. The hydrolysates with lowest IC50 values were further subjected to LC-MS-QTOF that revealed presence of 185 peptides. Selected peptides that had Peptide Ranker Score greater than 0.8 were further studied for prediction of possible interactions with enzyme markers: pancreatic lipase (PL) cholesterol esterase (CE) and angiotensin converting enzyme (ACE) using in silico analysis. The data generated suggested that most of the peptides could bind active site of PL while as only three peptides could bind active site of CE. Based on higher number of reactive residues in the bioactive peptides (BAP) and greater number of substrate binding sites, FCCLGPVPP was identified as potential CE inhibitory peptide while PAGNFLPPVAAAPVM, MLPLMLPFTMGY, and LRFPL were identified as PL inhibitors. While peptides PAGNFLP, FCCLGPVPP, PAGNFLMNGLMHR, PAVACCLPPLPCHM were identified as potential ACE inhibitors. Molecular docking of selected peptides showed hydrophilic and hydrophobic interactions between peptides and target enzymes. Moreover, due to the importance of renin in managing hypertension, peptides from hydrolysates with high ACE inhibiting potential were predicted for potential to interact with renin using in silico analysis. Molecular docking was subsequently employed to identify how the identified peptides, PVAAAPVM and LRPFL, could interact with renin and potentially inhibit it. Thus, non-bovine (camel) whey hydrolysates might be used as functional ingredients for production of functional foods with antihypertensive and anticholesterolemic properties.
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Triplett, Todd A., Kendra Triplett, Everett Stone, Michelle Zhang, Mark Manfredi, Candice Lamb, Yuri Tanno, Lauren Ehrlich, and George Georgiou. "Abstract 5571: Immune-checkpoint inhibition via enzyme-mediated degradation of kynurenine." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-5571.

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Kar, Saurajyoti, Shankarsan Ganai, Abhishek Dutta, Debjani Dutta, Surabhi Chaudhuri, Swapan Paruya, Samarjit Kar, and Suchismita Roy. "A sensitivity analysis study of enzyme inhibition kinetics through Cellular Automata." In INTERNATIONAL CONFERENCE ON MODELING, OPTIMIZATION, AND COMPUTING (ICMOS 20110). AIP, 2010. http://dx.doi.org/10.1063/1.3516319.

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"Inhibition of Carbohydrate Hydrolyzing Enzyme Activities by Flacourtia inermis Fruit Extracts." In International Conference on Agricultural, Ecological and Medical Sciences. International Institute of Chemical, Biological & Environmental Engineering, 2015. http://dx.doi.org/10.15242/iicbe.c0215117.

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Basharova, K. S., A. I. Bezrukova, E. V. Grigor’eva, G. V. Baydakova, S. V. Pavlova, I. V. Miliukhina, S. P. Medvedev, E. Yu Zakharova, S. N. Pchelina, and T. S. Usenko. "ALTERATION OF BIOCHEMICAL PARAMETERS OF LYSOSOMAL ACTIVITY UPON INHIBITION OF LRRK2 KINASE ACTIVITY IN CELL LINES FROM PATIENTS WITH PARKINSON’S DISEASE ASSOCIATED WITH MUTATIONS IN THE GBA1 GENE." In X Международная конференция молодых ученых: биоинформатиков, биотехнологов, биофизиков, вирусологов и молекулярных биологов — 2023. Novosibirsk State University, 2023. http://dx.doi.org/10.25205/978-5-4437-1526-1-296.

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The prospect of using LRRK2 inhibitors as treatment strategy for Parkinson’s disease (PD) associated with mutations in the gene GBA1 (GBA-PD), encoding the lysosomal enzyme glucocerebrosidase (GCase) is currently being discussed. We assessed the effectiveness of the LRRK2 kinase activity inhibitor MLi-2 in restoring GCase functions and the effect on the activity of other lysosomal enzymes in cell lines of patients with GBA-PD, LRRK2-PD.
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Reports on the topic "Enzyme inhibition"

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Jha, Ramesh Kumar. Engineering an Industrial Enzyme Chorismate lyase for Alleviated Product Inhibition. Office of Scientific and Technical Information (OSTI), March 2020. http://dx.doi.org/10.2172/1607901.

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Prochaska, David. Interfering with Zearalenone: Insights into Competitive Inhibition, Enzyme Interference, and Antioxidant Phytochemicals. Ames (Iowa): Iowa State University, May 2024. http://dx.doi.org/10.31274/cc-20240624-913.

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Farazi, Mena, Michael Houghton, Margaret Murray, and Gary Williamson. Systematic review of the inhibitory effect of extracts from edible parts of nuts on α-glucosidase activity. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, August 2022. http://dx.doi.org/10.37766/inplasy2022.8.0061.

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Review question / Objective: The aim of this review is to examine inhibitory effect of functional components in extracts from edible nuts on α-glucosidase activity. At the end of this review the following questions will be addressed by summarizing data of in-vitro studies: which nut extract has the strongest inhibitory effect? Which functional component (e.g. polyphenols) has the strongest inhibitory effect against α-glucosidase? Are there any differences between inhibition of α-glucosidase from different sources (e.g. yeast and mammalian)? Condition being studied: Any papers looking at inhibition of α-glucosidase activity (a carbohydrate digestive enzyme; includes sucrase, maltase and isomaltase activities) by extracts of edible parts of nut will be included in this review. Papers looking at other parts of nut plants and other enzymes will be excluded.
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Taylor, Palmer W. Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation. Fort Belvoir, VA: Defense Technical Information Center, May 2005. http://dx.doi.org/10.21236/ada442260.

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Taylor, Palmer W. Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation. Fort Belvoir, VA: Defense Technical Information Center, May 2004. http://dx.doi.org/10.21236/ada426549.

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Taylor, Palmer. Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation. Fort Belvoir, VA: Defense Technical Information Center, May 2003. http://dx.doi.org/10.21236/ada417075.

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Lurie, Susan, John Labavitch, Ruth Ben-Arie, and Ken Shackel. Woolliness in Peaches and Nectarines. United States Department of Agriculture, 1995. http://dx.doi.org/10.32747/1995.7570557.bard.

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The overall goal of the research was to understand the processes involved in the development of woolliness in peaches and nectarines. Four specific hypotheses were proposed and in the course of the research evidence was gathered t support two of them and to not support two others. The hypotheses and a summary of the evidence are outlined below. 1. That woolliness arises from an imbalance between the activities of the cell wall pectin degrading enzymes. Using 'Flavortop' nectarines and 'Hermoza' peaches as model systems, storage regimes were manipulated to induce or prevent woolliness. The expression (mRNA abundance), protein content (Western blotting), and activity of polygalacturonase (PG) and pectin esterase (PE) were followed. Expression of the enzymes was not different, but activity and the ratio between PG and PE activities were quite different in fruits developing woolliness or ripening normally. This was also examined by looking at the substrate, the pectin moiety of the cell wall, and i woolly fruit there were more high molecular weight pectins with regions of non-methylated galacturonic acid residues. Taking an in vitro approach it was found a) that PE activity was stable at 0oC while PG activity decreased; b) incubating the calcium pectate fraction of the cell wall with PE extracted from peaches caused the polymers to form a gel characteristic of the visual woolly symptoms in peaches. 2. That continued cell wall synthesis occurs during storage and contributes to structural changes i cell walls and improper dissolution and softening after storage. We tried to adapt our technique of adding 13C-glucose to fruit discs, which was used successfully to follow cell wall synthesis during tomato ripening. However, the difference in sugar content between the two fruits (4% in tomato and 12% in peach) meant that the 13C-glucose was much more diluted within the general metabolite pool. We were unable to see any cell wall synthesis which meant that either the dilution factor was too great, or that synthesis was not occurring. 3. That controlled atmosphere (CA) prevents woolliness by lowering all enzyme activities. CA was found to greatly reduce mRNA abundance of the cell wall enzymes compared to regular air storage. However, their synthesis and activity recovered during ripening after CA storage and did not after regular air storage. Therefore, CA prevented the inhibition of enzyme activation found in regular air storage. 4. That changes in cell wall turgor and membrane function are important events in the development of woolliness. Using a micro pressure probe, turgor was measured in cells of individual 'O'Henry' and 'CalRed' peaches which were woolly or healthy. The relationship between firmness and turgor was the same in both fruit conditions. These data indicate that the development and expression of woolliness are not associated with differences in membrane function, at least with regard to the factors that determine cell turgor pressure. In addition, during the period of the grant additional areas were explored. Encoglucanase, and enzyme metabolizing hemicellulose, was found to be highly expressed air stored, but not in unstored or CA stored fruit. Activity gels showed higher activity in air stored fruit as well. This is the first indication that other components of the cell wall may be involved in woolliness. The role of ethylene in woolliness development was also investigated at it was found a) that woolly fruits had decreased ability to produce ethylene, b) storing fruits in the presence of ethylene delayed the appearance of woolliness. This latter finding has implication for an inexpensive strategy for storing peaches and nectarines.
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Sadka, Avi, Mikeal L. Roose, and Yair Erner. Molecular Genetic Analysis of Citric Acid Accumulation in Citrus Fruit. United States Department of Agriculture, March 2001. http://dx.doi.org/10.32747/2001.7573071.bard.

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The acid content of the juice sac cells is a major determinant of maturity and fruit quality in citrus. Many citrus varieties accumulate acid in concentrations that exceed market desires, reducing grower income and consumer satisfaction. Pulp acidity is thought to be dependent on two mechanisms: the accumulation of citric acid in the vacuoles of the juice sac cells, and acidification of the vacuole. The major aim of the project was to direct effort toward understanding the mechanism of citric acid accumulation in the fruit. The following objectives were suggested: Measure the activity of enzymes likely to be involved in acid accumulation and follow their pattern of expression in developing fruit (Sadka, Erner). Identify and clone genes which are associated with high and low acid phenotypes and with elevated acid level (Roose, Sadka, Erner). Convert RAPD markers that map near a gene that causes low acid phenotype to specific co dominant markers (Roose). Use genetic co segregation to test whether specific gene products are responsible for low acid phenotype (Roose and Sadka). Objective 1 was fully achieved. Most of the enzymes of organic acid metabolism were cloned from lemon pulp. Their expression was studied during fruit development in low and high acid varieties. The activity and expression of citrate synthase, aconitase and NADP-isocitrate dehydrogenase (IDH) were studied in detail. The role that each enzyme plays in acid accumulation and decline was evaluated. As a result, a better understanding of the metabolic changes that contribute to acid accumulation was achieved. It was found that the activity of the mitochondrial aconitase is greatly reduced early in high-acid fruits, but not in acidless ones, suggesting that this enzyme plays an important role in acid accumulation. In addition, it was demonstrated that increases in the cytosolic forms of aconitase and NADP-IDH towards fruit maturation play probably a major role in acid decline. Our studies also demonstrated that the two mechanisms that contribute to fruit acidity, vacuolar acidification and citric acid accumulation, are independent, although they are tightly co-regulated. Additional, we demonstrated that sodium arsenite, which reduce fruit acidity, causes a transient inhibition in the activity of citrate synthase, but an induction in the gene expression. This part of the work has resulted in 4 papers. Objective 3 was also fully achieved. Using bulked segregant analysis, three random amplified polymorphic DNA (RAPD) markers were identified as linked to acitric, a gene controlling the acidless phenotype of pummelo 2240. One of them, which mapped 1.2 cM from acitric was converted into sequence characterized amplified region (SCAR marker, and into co dominant restriction length polymorphism (RFLP) marker. These markers were highly polymorphic among 59 citrus accessions, and therefore, they should be useful for selecting seedling progeny heterozygous for acitric in nearly all crosses between pummelo 2240 and other citrus genotypes. This part of the project resulted in one paper. Objective 4 was also fully achieved. Clones isolated by the Israeli group were sent to the American laboratory for co segregation analysis. However, none of them seemed to co segregate with the low acid phenotype. Both laboratories invested much effort in achieving the goals of Objective 2, namely the isolation of genes that are elevated in expression in low and high acid phenotypes, and in tissue cultures treated with arsenite (a treatment which reduces fruit acidity). However, conventional differential display and restriction fragment differential display analyses could not identify any differentially expressed genes. The isolation of such genes was the major aim of a continuation project, which was recently submitted.
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Granot, David, Scott Holaday, and Randy D. Allen. Enhancing Cotton Fiber Elongation and Cellulose Synthesis by Manipulating Fructokinase Activity. United States Department of Agriculture, 2008. http://dx.doi.org/10.32747/2008.7613878.bard.

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a. Objectives (a) Identification and characterization of the cotton fiber FRKs; (b) Generating transgenic cotton plants overproducing either substrate inhibited tomato FRK or tomato FRK without substrate inhibition; (c) Generating transgenic cotton plants with RNAi suppression of fiber expressed FRKs; (d) Generating Arabidopsis plants that over express FRK1, FRK2, or both genes, as additional means to assess the contribution of FRK to cellulose synthesis and biomass production. b. Background to the topic: Cellulose synthesis and fiber elongation are dependent on sugar metabolism. Previous results suggested that FRKs (fructokinase enzymes that specifically phosphorylate fructose) are major players in sugar metabolism and cellulose synthesis. We therefore hypothesized that increasing fructose phosphorylation may enhance fiber elongation and cellulose synthesis in cotton plants. Accordinlgy, the objectives of this research were: c. Major conclusions and achievements: Two cotton FRKs expressed in fibers, GhFRK2 and GhFRK3, were cloned and characterized. We found that GhFRK2 enzyme is located in the cytosol and GhFRK3 is located within plastids. Both enzymes enable growth on fructose (but not on glucose) of hexose kinase deficient yeast strain, confirming the fructokinase activity of the cloned genes. RNAi constructs with each gene were prepared and sent to the US collaborator to generate cotton plants with RNAi suppression of these genes. To examine the effect of FRKs using Arabidopsis plants we generated transgenic plants expressing either LeFRK1 or LeFRK2 at high level. No visible phenotype has been observed. Yet, plants expressing both genes simultaneously are being created and will be tested. To test our hypothesis that increasing fructose phosphorylation may enhance fiber cellulose synthesis, we generated twenty independent transgenic cotton plant lines overexpressing Lycopersicon (Le) FRK1. Transgene expression was high in leaves and moderate in developing fiber, but enhanced FRK activity in fibers was inconsistent between experiments. Some lines exhibited a 9-11% enhancement of fiber length or strength, but only one line tested had consistent improvement in fiber strength that correlated with elevated FRK activity in the fibers. However, in one experiment, seed cotton mass was improved in all transgenic lines and correlated with enhanced FRK activity in fibers. When greenhouse plants were subjected to severe drought during flowering and boll development, no genotypic differences in fiber quality were noted. Seed cotton mass was improved for two transgenic lines but did not correlate with fiber FRK activity. We conclude that LeFRK1 over-expression in fibers has only a small effect on fiber quality, and any positive effects depend on optimum conditions. The improvement in productivity for greenhouse plants may have been due to better structural development of the water-conducting tissue (xylem) of the stem, since stem diameters were larger for some lines and the activity of FRK in the outer xylem greater than observed for wild-type plants. We are testing this idea and developing other transgenic cotton plants to understand the roles of FRK in fiber and xylem development. We see the potential to develop a cotton plant with improved stem strength and productivity under drought for windy, semi-arid regions where cotton is grown. d. Implications, scientific and agricultural: FRKs are probably bottle neck enzymes for biomass and wood synthesis and their increased expression has the potential to enhance wood and biomass production, not only in cotton plants but also in other feed and energy renewable plants.
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Blumwald, Eduardo, and Avi Sadka. Sugar and Acid Homeostasis in Citrus Fruit. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7697109.bard.

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Citrus fruit quality standards have been determined empirically, depending on species and on the particular growing regions. In general, the TSS (total soluble solids) to total acidity (TA) ratio determines whether citrus fruit can be marketed. Soluble sugars account for most of the TSS during harvest while TA is determined almost solely by the citric acid content, which reaches levels of 1-5% by weight in many cultivated varieties. Acid and sugar homeostasis in the fruit is critical for the management of existing cultivars, the development of new cultivars, the improvement of pre- and post-harvest strategies and the control of fruit quality and disorders. The current proposal (a continuation of a previous proposal) aimed at: (1) completing the citrus fruit proteome and metabolome, and establish a citrus fruit functional database, (2) further characterization of the control of fruit acidity by studying the regulation of key steps affecting citrate metabolism, and determine the fate of citrate during acid decline stage, and (3) Studying acid and sugar homeostasis in citrus fruits by characterizing transport mechanisms across membranes. These aims were completed as the following: (1) Our initial efforts were aimed at the characterization and identification of citric acid transporters in citrus juice cells. The identification of citrate transporters at the vacuole of the citrus juice cell indicated that the steady-state citrate cytosolic concentration and the action of the cytosolic aconitase were key elements in establishing the pH homeostat in the cell that regulates the metabolic shift towards carbon usage in the fruit during the later stages of fruit development. We focused on the action of aconitase, the enzyme mediating the metabolic use of citric acid in the cells, and identified processes that control carbon fluxes in developing citrus fruits that control the fruit acid load; (2) The regulation of aconitase, catalyzing a key step in citrate metabolism, was further characterized by using two inhibitors, citramalte and oxalomalte. These compounds significantly increased citrate content and reduced the enzyme’s activity. Metabolite profiling and changes of amino-acid metabolizing enzymes in oxalomalate- treated cells suggested that the increase in citrate, caused by aconitase inhibition, induces amino acid synthesis and the GABA shunt, in accordance with the suggested fate of citrate during the acid decline stage in citrus fruit. (3) We have placed a considerable amount of time on the development of a citrus fruit proteome that will serve to identify all of the proteins in the juice cells and will also serve as an aid to the genomics efforts of the citrus research community (validating the annotation of the fruit genes and the different ESTs). Initially, we identified more than 2,500 specific fruit proteins and were able to assign a function to more than 2,100 proteins (Katz et al., 2007). We have now developed a novel Differential Quantitative LC-MS/MS Proteomics Methodology for the identification and quantitation of key biochemical pathways in fruits (Katz et al., 2010) and applied this methodology to identify determinants of key traits for fruit quality (Katz et al., 2011). We built “biosynthesis maps” that will aid in defining key pathways associated with the development of key fruit quality traits. In addition, we constructed iCitrus (http://wiki.bioinformatics.ucdavis.edu/index.php/ICitrus), a “functional database” that is essentially a web interface to a look-up table that allows users to use functional annotations in the web to identify poorly annotated citrus proteins. This resource will serve as a tool for growers and field extension specialists.
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