Citrate Synthesis Research Articles

Synthesis and characterization of Tamoxifen citrate modified reduced graphene oxide nano sheets for breast cancer therapy

Theranostic agents are of immense consideration in the current generation nanomedicine. In this study, we have developed a facile approach for the fabrication of Tamoxifen citrate modified nanosized reduced graphene oxide (nano-rGO) with more stability and low cytotoxicity. The prepared nano-rGO sheets were characterized using HR-TEM and AFM imaging techniques. Further, the cytotoxicity was assessed using MTT assay on female BALB/c nude mice MCF-7 cell lines. In addition, by means of continuous-wave near-infrared laser, cancer cells in vivo were significantly ablated because of the photothermal effect stimulated by tamoxifen modified nano-rGO. These results indicated that the prepared tamoxifen modified nano-rGO has the ability to apply in the photothermal therapy of breast cancers. Consequently, further exploration of photothermal therapeutics is desirable for the synthesis of novel nano materials with additional functionalities.

Highly Selective Catalytic Properties of HZSM-5 Zeolite in the Synthesis of Acetyl Triethyl Citrate by the Acetylation of Triethyl Citrate with Acetic Anhydride

The catalytic activities of acid catalysts for the acetylation of triethyl citrate with acetic anhydride in the preparation of acetyl triethyl citrate were evaluated. Microporous zeolites such as HZSM-5 and HY zeolites catalysts were introduced as heterogeneous acid catalysts. HZSM-5 zeolite catalysts showed a high conversion of triethyl citrate and excellent selectivity of acetyl triethyl citrate. The catalytic activities of HZSM-5 zeolites were superior to those of the HY zeolites. In particular, the selectivity of acetyl triethyl citrate on HZSM-5 zeolites exceeded 95%. The moderate acid strength of HZSM-5 (Si/Al = 75) zeolite led to the highest catalytic activities among the HZSM-5 zeolite catalysts, which have various acid strengths.

An Operationally Simple Synthesis of Fentanyl Citrate

Fentanyl is a synthetic opioid developed by Janssen and co-workers over 40 years ago and is currently used for chronic pain management.1 The medical importance of fentanyl has inspired synthetic in...

Aluminum induced physiological and proteomic responses in tea (Camellia sinensis) roots and leaves

Tea (Camellia sinensis (L.) O. Kuntze), is an aluminum (Al) hyperaccumulator and grows well in acid soils. Although Al-induced growth of tea plant has been studied, the proteomic profiles of tea plants in response to Al are unclear. In the present study, the proteomic profiles in tea roots and leaves under Al stress were investigated using iTRAQ proteomics approach. In total, 755 and 1059 differentially expressed proteins were identified in tea roots and leaves, respectively. KEGG enrichment analysis showed that the differentially expressed proteins in roots were mainly involved in 11 pathways whereas those from leaves were mainly involved in 9 pathways. Abundance of most protein functions in glycolytic metabolism were enhanced in tea roots, and proteins involved in photosynthesis were stimulated in tea leaves. The protein ferulate-5-hydroxylase (F5H) in lignin biosynthetic pathway was down-regulated in both roots and leaves. Furthermore, antioxidant enzymes (ascorbate peroxidase, catalase and glutathione S-transferase) and citrate synthesis were accumulated in tea roots in response to Al. The results indicated that active photosynthesis and glycolysis as well as increased activities of antioxidant enzymes can be considered as a possible reason for the stimulatory effects of Al on the growth of tea plants. Additionally, the down-regulation of F5H and the binding of Al and phenolic acids may reduce the accumulation of lignin.

Comparative genomics and transcriptome analysis of Aspergillus niger and metabolic engineering for citrate production

Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains—namely, A. niger H915-1 (citrate titer: 157 g L−1), A1 (117 g L−1), and L2 (76 g L−1)—to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis. Furthermore, transcriptome analysis of A. niger H915-1 revealed that the transcription levels of 479 genes changed between the cell growth stage (6 h) and the citrate synthesis stage (12 h, 24 h, 36 h, and 48 h). In the glycolysis pathway, triosephosphate isomerase was up-regulated, whereas pyruvate kinase was down-regulated. Two cytosol ATP-citrate lyases, which take part in the cycle of citrate synthesis, were up-regulated, and may coordinate with the alternative oxidases in the alternative respiratory pathway for energy balance. Finally, deletion of the oxaloacetate acetylhydrolase gene in H915-1 eliminated oxalate formation but neither influence on pH decrease nor difference in citrate production were observed.

Continuous flow synthesis of citrate capped gold nanoparticles using UV induced nucleation

A novel multimodal reactor system for separating the nucleation and growth phases of gold nanoparticle synthesis to control particle size.

Sustainable Catalytic Process for Synthesis of Triethyl Citrate Plasticizer over Phosphonated USY Zeolite

Fruits wastage is harmful to health and environment concerning spreading diseases and soil pollution, respectively. To avoid this issue, use of citrus fruit waste for the production of citric acid (CA) is one of viable mean to obtain value added chemicals. Moreover, synthesis of triethyl citrate (TEC), a non-toxic plasticizer by esterification of CA with ethanol over heterogeneous catalyst would be renewable and sustainable catalytic process. In this context, parent Ultrastable Y (USY) and different percentage phosphonated USY (P-USY) zeolites were used for the synthesis of TEC in a closed batch reactor, for the first time. The synthesized catalysts were characterized by N2-adsorption desorption isotherm, powder X-ray diffraction (XRD) and NH3 temperature programmed desorption (TPD. Effect of reaction conditions, such as the molar ratio of ethanol to CA (5:1 - 20:1), the catalyst to CA ratio (0.05 - 0.25) and reaction temperature (363-403 K), were studied in view to maximizing CA conversion and TEC yield. Phosphonated USY catalysts were found to be superior in activity (CA conversion and TEC yield) than parent USY, which is attributed to the increased in total acidity with phosphonation. Among the studied catalysts, the P2USY (2% phosphorous loaded on USY) was found to be an optimum catalyst with 99% CA conversion and 82% TEC yield, which is higher than the reported values. This study opens new avenues of research demonstrating principles of green chemistry such as easy separable and reusable catalyst, non-toxic product, bio-renewable synthetic route, milder operating parameters and waste minimization.

Citrate as a possible iron-pooling substance in the marine diatom Thalassiosira pseudonana

An iron (Fe)-binding substance (FeBS) was sought for the marine diatom Thalassiosira pseudonana, because the organism is devoid of a gene that encodes the predominant Fe storage protein ferritin. High-performance liquid chromatography–inductively coupled plasma/emission mass spectrometry (HPLC-ICP/MS) analysis of an extract of diatom cells indicated the presence of an FeBS specific to the cells grown in Fe-replete medium. Heat treatment followed by anion-exchange chromatography with monitoring of Fe(III)-dissolving activity was used to isolate the FeBS from the cell extract. Structural analysis using 1H NMR spectrometry demonstrated that the FeBS was composed of citrate. In addition, HPLC-ICP/MS together with ESI–MS demonstrated that the FeBS was likely a triferric tricitrate complex. Although the citrate content of the diatom cells was enhanced according to the Fe nutritional status of the medium, this phenomenon seemed to occur by an indirect mechanism, as a previous report demonstrated a reduced citrate content in T. pseudonana cells grown in Fe-replete medium (Bromke et al. in Plos One doi: 10.1371/journal.pone.0067340, 2013). It is most likely that, based on the extended Redfield ratio 121(C):16(N):1(P):0.0075(Fe), the culture used in the current study may have suffered from nutrient deficiency of a major element, such as nitrogen. Such a situation may occur frequently for this open sea diatom. As windblown dust is a prevailing Fe source for the open oceanic diatom T. pseudonana, a rapid elevation in Fe concentration in the seawater can render the cells nitrogen deficient, causing enhanced citrate synthesis and resulting in the formation of a triferric tricitrate complex as Fe storage machinery.

The contribution of stored malate and citrate to the substrate requirements of metabolism of ripening peach (Prunus persica L. Batsch) flesh is negligible. Implications for the occurrence of phosphoenolpyruvate carboxykinase and gluconeogenesis

The first aim of this study was to determine the contribution of stored malate and citrate to the substrate requirements of metabolism in the ripening flesh of the peach (Prunus persica L. Batsch) cultivar Adriatica. In the flesh, stored malate accumulated before ripening could contribute little or nothing to the net substrate requirements of metabolism. This was because there was synthesis and not dissimilation of malate throughout ripening. Stored citrate could potentially contribute a very small amount (about 5.8%) of the substrate required by metabolism when the whole ripening period was considered, and a maximum of about 7.5% over the latter part of ripening. The second aim of this study was to investigate why phosphoenolpyruvate carboxykinase (PEPCK) an enzyme utilised in gluconeogenesis from malate and citrate is present in peach flesh. The occurrence and localisation of enzymes utilised in the metabolism of malate, citrate and amino acids were determined in peach flesh throughout its development. Phosphoenolpyruvate carboxylase (essential for the synthesis of malate and citrate) was present in the same cells and at the same time as PEPCK and NADP-malic enzyme (both utilised in the dissimilation of malate and citrate). A hypothesis is presented to explain the presence of these enzymes and to account for the likely occurrence of gluconeogenesis.

Acceleration effect of copper(II) ions on the rate of citrate synthesis of gold nanoparticles

The gold nanoparticles (GNPs) were obtained by modification of the classical Turkevich citrate method by the addition of copper(II) ions in the initial reaction mixture. We studied the kinetics of the nanoparticles growth with or without copper(II) ions, synthesized at two different temperatures. The kinetic curves obtained by means of UV–vis spectroscopy from the plasmon maxima demonstrated the acceleration effects of the copper(II) ions on nucleation and growth of the GNPs. These effects were also confirmed from the Atomic Force Microscope (AFM) imaging data where the AFM was applied as a tool for studying the kinetics of the GNPs’ growth. From the analysis of AFM images in the course of the synthesis process were obtained the sizes (i.e., diameters) of the GNPs and the GNPs’ growth profiles were fitted with the Finke–Watzky (F–W) kinetic model. From the experimental data and the theoretical fits we found that the citrate reduction of the tetrachloroauric acid was accelerated by the addition of copper(II) ions as well as the GNPs’ growth was accelerated following the F–W kinetics model. Using Transmission Electron Microscopy (TEM) we compared the morphology and the size distribution of the nanoparticles synthesized by the citrate method with or without copper(II) ions. The results showed that the addition of copper(II) ions in the initial reaction mixture of the Turkevich citrate synthesis let to acceleration of both the nucleation and the growth processes following the F–W kinetic model.

Glycol–citrate synthesis of ultrafine lanthanum zirconate

The effect of concentrations of organic components (ethylene glycol and citric acid) on the intensity of redox reaction and the properties of the product in the glycol citrate synthesis of ultrafine lanthanum zirconate La2Zr2O7 has been studied. The onset and offset temperatures of the fluorite–pyrochlore phase transition have been outlined. Oxide particle coarsening upon high-temperature treatment is studied.

Extracellular Citrate in Health and Disease.

Citrate is one of the major substrates for intracellular metabolism. The extracellular level of citrate is stable in blood but varies locally, with slightly increased levels in brain and high levels in prostate. Recent metabolomics research suggests that citrate level is a potential harbinger of different pathophysiological states; its decrease has been correlated with male infertility, brain diseases and metastatic cancer. In this review we discuss the role of citrate as an energy substrate for sperm. We also review the function of citrate released by astrocytes in the normal operation of neurons, and consequently we suggest a potential role of neuronal plasma membrane citrate transporters in mental disorders. Finally, we review recent relevant publications studying blood, urine and tissue citrate levels in cancer patients and hypothesize that extracellular citrate supports cancer cell metabolism critical for metastasis. Despite the importance of extracellular citrate in physiological and pathophysiological processes, surprisingly little is known about citrate synthesis in specialized cells, or about citrate transporters controlling citrate movement across various membranes. Determination of the molecular origin of citrate transporters in astrocytes, sperm and cancer cells could offer novel therapeutic targets and the possibility to pharmacologically regulate citrate release and uptake for preventing male infertility, treating mental diseases and targeting cancer.

Metabolic characteristics of citric acid synthesis by the fungus Aspergillus niger

The article discusses recent advances in the study of the metabolism of Aspergillus niger, a producer of citric acid, and some of its characteristics that may be responsible for the overproduction of citric acid. The paper is designed so that the entire process of citrate biosynthesis, from the absorption of glucose from a nutrient medium to the extraction of citric acid from cells, is divided into stages that are critical for the yield of the desired product. This arrangement of the material makes it possible to show the main regulatory steps in the chain of citrate synthesis. Influencing these steps enables regulation of the biosynthesis of citric acid at the level of cellular metabolism. This eventually opens promising avenues in the improvement of producing strains by means of genetic engineering. The paper also reviews the influence of some fermentation conditions (medium components, additives, and technological parameters) on metabolic processes in producing cells, which is important for an integral understanding of both biosynthesis process at the cellular level and fermentation technology.

Incorporation of Jahn-Teller Cu(2+) Ions into Magnetoelectric Multiferroic MnWO4: Structural, Magnetic, and Dielectric Permittivity Properties of Mn1-xCuxWO4 (x ≤ 0.25).

Polycrystalline samples of Mn1-xCuxWO4 (x ≤ 0.5) have been prepared by a solid-state synthesis as well as from a citrate synthesis at moderate temperature (850 °C). The goal is to study changes in the structural, magnetic, and dielectric properties of magnetoelectric type-II multiferroic MnWO4 caused by replacing Jahn-Teller-inactive Mn(2+) (d(5), S = 5/2) ions with Jahn-Teller-active Cu(2+) (d(9), S = 1/2) ions. Combination of techniques including scanning electron microscopy, powder X-ray and neutron diffraction, and Raman spectroscopy demonstrates that the polycrystalline samples with low copper content 0 ≤ x ≤ 0.25 are solid solution that forms in the monoclinic P2/c space group. Rietveld analyses indicate that Cu atoms substitutes for Mn atoms at the Mn crystallographic site of the MnWO4 structure and suggest random distributions of Jahn-Teller-distorted CuO6 octahedra in the solid solution. Magnetic susceptibility reveals that only 5% of Cu substitution suppresses the nonpolar collinear AF1 antiferromagnetic structure observed in pure MnWO4. Type-II multiferroicity survives a weak Cu substitution rate (x < 0.15). Multiferroic transition temperature and Néel temperature increase as the amount of Cu increases. New trends in some of the magnetic properties and in dielectric behaviors are observed for x = 0.20 and 0.25. Careful analysis of the magnetic susceptibility reveals that the incorporation of Cu into MnWO4 strengthens the overall antiferromagnetic interaction and reduces the magnetic frustration.

A Facile, Improved Synthesis of Sildenafil and Its Analogues.

This paper describes the facile synthesis of sildenafil citrate (1) and its related compounds through an improved chlorosulfonation reaction using chlorosulfonic acid and thionyl chloride. This synthesis results in pure sildenafil with high yield. The structures of the compounds were determined with infrared (IR), 1H-NMR and 13C-NMR spectroscopic methods, and high resolution mass spectroscopy (HRMS) analysis.

Integrated, Step-Wise, Mass-Isotopomeric Flux Analysis of the TCA Cycle

Mass isotopomer multi-ordinate spectral analysis (MIMOSA) is a step-wise flux analysis platform to measure discrete glycolytic and mitochondrial metabolic rates. Importantly, direct citrate synthesis rates were obtained by deconvolving the mass spectra generated from [U-(13)C6]-D-glucose labeling for position-specific enrichments of mitochondrial acetyl-CoA, oxaloacetate, and citrate. Comprehensive steady-state and dynamic analyses of key metabolic rates (pyruvate dehydrogenase, β-oxidation, pyruvate carboxylase, isocitrate dehydrogenase, and PEP/pyruvate cycling) were calculated from the position-specific transfer of (13)C from sequential precursors to their products. Important limitations of previous techniques were identified. In INS-1 cells, citrate synthase rates correlated with both insulin secretion and oxygen consumption. Pyruvate carboxylase rates were substantially lower than previously reported but showed the highest fold change in response to glucose stimulation. In conclusion, MIMOSA measures key metabolic rates from the precursor/product position-specific transfer of (13)C-label between metabolites and has broad applicability to any glucose-oxidizing cell.

Effects of Lysiphlebia japonica (Ashmead) on cotton-melon aphid Aphis gossypii Glover lipid synthesis.

The cotton-melon aphid, Aphis gossypii Glover, is a major insect pest worldwide. The wasp Lysiphlebia japonica (Ashmead) is the predominant parasitoid of cotton-melon aphids in north China. Parasitization has been reported to affect host lipids in several systems, but the lipid synthesis-related genes and transcription changes in the cotton-melon aphid-parasitoid interaction are not clear. In this study, 36 lipid synthesis-related genes were cloned and their transcription changes in parasitized aphids were studied by quantitative real-time PCR. In parasitized cotton-melon aphids, almost all key genes in the glycerolipid synthesis pathway were up-regulated, the rate-limiting enzyme diacylglycerol o-acyltransferase by 3.24-fold. The rate-limiting enzyme of the glycolytic pathway, pyruvate kinase, and the pace-making enzyme in citrate synthesis were 1.69-fold and 1.75-fold less in parasitized aphids than in unparasitized aphids, respectively. These results suggest increased glycerolipid synthesis in parasitized aphids but that citrate production from sucrose was decreased. Aconitate hydratase (aco), in the pathway that converts amino acids into citrate, was up-regulated. The number of fragments per kilobase per million mapped reads of the mitochondrial aco2 gene was only 4.6, whereas that of the cytoplasmic aco1 was 41.5, indicating that the citrate comes from amino acids in the cytoplasm of parasitized cotton-melon aphids.

ChemInform Abstract: Crystal Structure, Magnetic Properties and Advances in Hexaferrites: A Brief Review

AbstractReview: 22 refs.

Phosphoenolpyruvate Carboxylase in Arabidopsis Leaves Plays a Crucial Role in Carbon and Nitrogen Metabolism.

Phosphoenolpyruvate carboxylase (PEPC) is a crucial enzyme that catalyzes an irreversible primary metabolic reaction in plants.Previous studies have used transgenic plants expressing ectopic PEPC forms with diminished feedback inhibition to examine the role of PEPC in carbon and nitrogen metabolism. To date, the in vivo role of PEPC in carbon and nitrogen metabolism has not been analyzed in plants. In this study, we examined the role of PEPC in plants, demonstrating that PPC1 and PPC2 were highly expressed genes encoding PEPC in Arabidopsis (Arabidopsis thaliana) leaves and that PPC1 and PPC2 accounted for approximately 93% of total PEPC activity in the leaves. A double mutant, ppc1/ppc2, was constructed that exhibited a severe growth-arrest phenotype. The ppc1/ppc2 mutant accumulated more starch and sucrose than wild-type plants when seedlings were grown under normal conditions. Physiological and metabolic analysis revealed that decreased PEPC activity in the ppc1/ppc2 mutant greatly reduced the synthesis of malate and citrate and severely suppressed ammonium assimilation. Furthermore, nitrate levels in the ppc1/ppc2 mutant were significantly lower than those in wild-type plants due to the suppression of ammonium assimilation. Interestingly, starch and sucrose accumulation could be prevented and nitrate levels could be maintained by supplying the ppc1/ppc2 mutant with exogenous malate and glutamate, suggesting that low nitrogen status resulted in the alteration of carbon metabolism and prompted the accumulation of starch and sucrose in the ppc1/ppc2 mutant. Our results demonstrate that PEPC in leaves plays a crucial role in modulating the balance of carbon and nitrogen metabolism in Arabidopsis.

Metabolic Tracing Using Stable Isotope-Labeled Substrates and Mass Spectrometry in the Perfused Mouse Heart.

There has been a resurgence of interest for the field of cardiac metabolism catalyzed by evidence demonstrating a role of metabolic dysregulation in the pathogenesis of heart disease as well as the increased need for new therapeutic targets for patients with these diseases. In this regard, measuring substrate fluxes is critical in providing insight into the dynamics of cellular metabolism and in delineating the regulation of metabolite production and utilization. This chapter provides a comprehensive description of concepts, guidelines, and tips to assess metabolic fluxes relevant to energy substrate metabolism using (13)C-labeled substrates and (13)C-isotopomer analysis by gas chromatography-mass spectrometry (GC-MS), and the ex vivo working heart as study model. The focus will be on the mouse and on flux parameters, which are commonly assessed in the field, namely, those relevant to substrate selection for energy metabolism, specifically the relative contribution of carbohydrate (glucose, lactate, and pyruvate) and fatty acid oxidation to acetyl-CoA formation for citrate synthesis, glycolysis, as well as anaplerosis. We provide detailed procedures for the heart isolation and perfusion in the working mode as well as for sample processing for metabolite extraction and analysis by GC-MS and subsequent data processing for calculation of metabolic flux parameters. Finally, we address practical considerations and discuss additional applications and future challenges.