Aldose Sugars Research Articles

Modulation and Tuning of UiO-66 for Lewis Acid Catalyzed Carbohydrate Conversion: Conversion of Unprotected Aldose Sugars to Polyhydroxyalkyl and C-Glycosyl Furans

Modulation and Tuning of UiO-66 for Lewis Acid Catalyzed Carbohydrate Conversion: Conversion of Unprotected Aldose Sugars to Polyhydroxyalkyl and <i>C</i>-Glycosyl Furans

A thermodynamic atlas of carbon redox chemical space

Redox biochemistry plays a key role in the transduction of chemical energy in living systems. However, the compounds observed in metabolic redox reactions are a minuscule fraction of chemical space. It is not clear whether compounds that ended up being selected as metabolites display specific properties that distinguish them from nonbiological compounds. Here, we introduce a systematic approach for comparing the chemical space of all possible redox states of linear-chain carbon molecules to the corresponding metabolites that appear in biology. Using cheminformatics and quantum chemistry, we analyze the physicochemical and thermodynamic properties of the biological and nonbiological compounds. We find that, among all compounds, aldose sugars have the highest possible number of redox connections to other molecules. Metabolites are enriched in carboxylic acid functional groups and depleted of ketones and aldehydes and have higher solubility than nonbiological compounds. Upon constructing the energy landscape for the full chemical space as a function of pH and electron-donor potential, we find that metabolites tend to have lower Gibbs energies than nonbiological molecules. Finally, we generate Pourbaix phase diagrams that serve as a thermodynamic atlas to indicate which compounds are energy minima in redox chemical space across a set of pH values and electron-donor potentials. While escape from thermodynamic equilibrium toward kinetically driven states is a hallmark of life and its origin, we envision that a deeper quantitative understanding of the environment-dependent thermodynamic landscape of putative prebiotic molecules will provide a crucial reference for future origins-of-life models.

Conversion of Unprotected Aldose Sugars to Polyhydroxyalkyl and C-Glycosyl Furans via Zirconium Catalysis.

An efficient, zirconium-catalyzed conversion of unprotected aldose sugars with acetylacetone to polyhydroxyalkyl furans or C-glycosylfurans is reported. The furan products are formed in up to 93% yield using 5-10 mol % ZrCl4. Pentoses are readily converted at room temperature, while hexoses and their oligosaccharides require mild heating (i.e., 50 °C). Efficient conversions of glycolaldehyde, glyceraldehyde, erythrose, a heptose, and glucosamine are also demonstrated. This approach outpaces each of the previous Lewis acid-catalyzed methods in at least one the following ways: (i) lower catalyst loadings; (ii) reduced reaction temperatures; (iii) shorter reaction times; (iv) equimolar substrate stoichiometry; (v) expanded sugar scope; (vi) higher selectivities; and (vii) the use of an Earth-abundant Zr catalyst.

UV Fluorescence-Based Determination of Urinary Advanced Glycation End Products in Patients with Chronic Kidney Disease.

Advanced glycation end products (AGEs) are a class of proteins or lipids that are non-enzymatically glycated and oxidized after contact with aldose sugars. The accumulation of AGEs results in carbonyl stress, which is characteristic for diabetes mellitus, uremia, atherosclerosis and vascular dysfunction. In recent decades, several innovative methods have been developed to measure the concentration of AGEs in blood or urine. In the present study, we evaluated the use of UV fluorescence as an alternative tool to detect urinary AGEs in four groups of well characterized chronic kidney disease (CKD) patients over a wide range of kidney insufficiency and in a group of healthy subjects. Using an excitation wavelength of 365 nm, the fluorescence spectra of urinary AGEs were recorded in the 400–620 nm emission range. When considering the emission peaks at 440 nm and 490 nm, a significantly higher AGE-specific fluorescence intensity was detected in CKD patients compared to healthy subjects (p < 0.0001 and p = 0.0001, respectively). The urinary creatinine adjusted fluorescence emission spectra in the group of CKD patients with diabetes mellitus were comparable with those of CKD patients without diabetes mellitus. Creatinine-adjusted fluorescence emission spectra were highest in CKD patients with proteinuria, moderate in CKD patients without proteinuria and lowest in healthy controls (p < 0.0001 at both emission wavelengths). In a multiple regression analysis, age, CRP and insulin treatment were predictors of fluorescence intensity at the emission wavelength of 440 nm. Age and insulin treatment were predictors at 490 nm. The presented method is a simple, cheap, alternative method to monitor the AGE-load in the CKD population.

Synthesis and Anticancer Activity of New ((Furan-2-yl)-1,3,4-thiadiazolyl)-1,3,4-oxadiazole Acyclic Sugar Derivatives.

New sugar hydrazones incorporating furan and/or 1,3,4-thiadiazole ring systems were synthesized by reaction of the corresponding hydrazide with different aldose sugars. Heterocyclization of the formed hydrazones afforded the derived acyclic nucleoside analogues possessing the 1,3,4-oxadiazoline as modified nucleobase via acetylation followed by the heterocyclization process. The anticancer activity of the synthesized compounds was studied against human liver carcinoma cell (HepG-2) and at human normal retina pigmented epithelium cells (RPE-1). High activities were revealed by compounds 3, 12 and 14 with IC50 values near to that of the reference drug doxorubicin.

Mesoporous manganese oxide/manganese ferrite nanopopcorns with dual enzyme mimic activities: A cascade reaction for selective detection of ketoses

Nanomaterials possessing enzyme-like activity have been extensively studied owing to their high stability and tunable catalytic properties. In this work, a simple method has been developed for the synthesis of porous manganese oxide/manganese ferrite (MnOx/MnFe2O4) nanopopcorns (MFNPs) in neutral media. The MFNPs exhibit dual enzymatic activities towards selective oxidation of ketoses followed by H2O2-induced decline of its catalytic activity. MFNPs, with MnFe2O4 as the core material and an outer layer rich in MnOx, were synthesized from ammonium iron(III) citrate and potassium permanganate at 70 °C for 12 h followed by annealing at 300 °C for 6 h. The nanozyme, MFNPs, exhibited oxidase-like activity, which was proved by the oxidation of amplex red (AR) in the presence of dissolved oxygen in the solution, to form fluorescent resorufin. The activity of MFNPs is highly suppressed by H2O2 as a result of its induced dissolution of MnOx. In addition, MFNPs having catalytic activity towards the selective oxidation of ketoses (e.g., fructose) followed by the formation of H2O2. The as-formed H2O2 diminished the catalytic activity of MFNPs for the AR oxidation to form fluorescent resorufin. Upon increasing fructose concentration, the fluorescence of resorufin decreases. Since the MFNPs do not show catalytic activity towards aldose sugars, such as glucose, sucrose, and mannose, the AR/MFNPs probe has high selectivity and sensitivity for detection of fructose with a limit of detection of 32 μM. Our study shows its great potential for quantitation of fructose in honey samples.

Identification of a mutarotase gene involved in D-galactose utilization in Aspergillus nidulans

Aldose 1-epimerases or mutarotases (EC 5.1.3.3) are catalyzing the interconversion of α- and β-anomers of hemiacetals of aldose sugars such as D-glucose and D-galactose, and are presumed to play an auxiliary role in carbohydrate metabolism as mutarotation occurs spontaneously in watery solutions. The first step in the Leloir pathway of D-galactose breakdown is preceded by accelerated conversion of β-D-galactopyranose into the α-anomer, the substrate of the anomer-specific D-galactose 1-kinase. Here, we identified two putative aldose-1-epimerase genes (galmA and galmB) in the model organism Aspergillus nidulans, and characterized them upon generation of single- and double deletion mutant strains, as well as overexpressing mutants carrying multiple copies of either. Assaying cell-free extracts from the galmB single- and galm double mutants, we observed that the mutarotation hardly exceeded spontaneous anomer conversion, while galmB multicopy strains displayed higher activities than the wild type, increasing with the copy number. When grown on D-galactose in submerged cultures, biomass formation and D-galactose uptake rates in mutants lacking galmB were considerably reduced. None such effects were observed studying galmA deletion mutants, which consistently behave like the wild type. We conclude that GalmB is the physiologically relevant mutarotase for the utilization of D-galactose in A. nidulans.

Effect of redox properties of LaCoO3 perovskite catalyst on production of lactic acid from cellulosic biomass

Cost-effective conversion of cellulosic biomass to value-added lactic acid with heterogeneous catalysts has attracted much attention recent years. While both solid Lewis acids and bases have been extensively studied, the role of redox catalysts for the production of lactic acid is barely understood. Herein, the LaCoO3 perovskite metal oxides with strong redox properties and a good stability in hydrothermal media were used as the catalysts for the conversion of a variety of cellulosic biomass to lactic acid. The effects of reaction conditions such as reaction temperature, catalyst loading, and gas atmosphere were investigated. At the optimum conditions, the yields of approximately 40%, 38%, and 24% lactic acid were obtained from glucose, xylose and cellulose, respectively. The key intermediates such as pyruvic acid were used as the probe reactants to explore the reaction mechanism. Unlike Lewis acid or base catalysed sugar conversion reactions, the redox pathway might start from the oxidative decarboxylation of aldose sugars and the lattice oxygen atoms in the LaCoO3 perovskite structure participate the redox cycles in the conversion of sugars to lactic acid. Lastly, the stability of the LaCoO3 catalyst in hydrothermal reaction media was discussed.

Characterization of a unique Caulobacter crescentus aldose-aldose oxidoreductase having dual activities.

We describe here the characterization of a novel enzyme called aldose-aldose oxidoreductase (Cc AAOR; EC 1.1.99) from Caulobacter crescentus. The Cc AAOR exists in solution as a dimer, belongs to the Gfo/Idh/MocA family and shows homology with the glucose-fructose oxidoreductase from Zymomonas mobilis. However, unlike other known members of this protein family, Cc AAOR is specific for aldose sugars and can be in the same catalytic cycle both oxidise and reduce a panel of monosaccharides at the C1 position, producing in each case the corresponding aldonolactone and alditol, respectively. Cc AAOR contains a tightly-bound nicotinamide cofactor, which is regenerated in this oxidation-reduction cycle. The highest oxidation activity was detected on D-glucose but significant activity was also observed on D-xylose, L-arabinose and D-galactose, revealing that both hexose and pentose sugars are accepted as substrates by Cc AAOR. The configuration at the C2 and C3 positions of the saccharides was shown to be especially important for the substrate binding. Interestingly, besides monosaccharides, Cc AAOR can also oxidise a range of 1,4-linked oligosaccharides having aldose unit at the reducing end, such as lactose, malto- and cello-oligosaccharides as well as xylotetraose. (1)H NMR used to monitor the oxidation and reduction reaction simultaneously, demonstrated that although D-glucose has the highest affinity and is also oxidised most efficiently by Cc AAOR, the reduction of D-glucose is clearly not as efficient. For the overall reaction catalysed by Cc AAOR, the L-arabinose, D-xylose and D-galactose were the most potent substrates.

Challenges of and Insights into Acid-Catalyzed Transformations of Sugars

The selective transformation of hexose and pentose sugars to intermediate platform chemicals, such as furans, is an essential step in the conversion of cellulosic and hemicellulosic biomass to biofuels and biochemicals. Yet, many challenges in achieving commercially viable processes remain. In this feature article, we outline challenges that need to be overcome to enable these transformations. Then, we present the newly introduced acid-catalyzed isomerization of aldose sugars to ketose sugars via a class of solid Lewis acid catalysts (e.g., Sn-Beta, Ti-Beta). We elucidate mechanistic insights arising from subnanometer cooperativity and solvent effects that can be controlled to tune reaction pathways and selectivity and draw parallels between heterogeneous and homogeneous Lewis acid catalysts. Subsequently, we discuss fructose dehydration to 5-hydroxyl-methylfurfural (HMF) via homogeneous and heterogeneous Bronsted acid-catalyzed chemistry. We show how fundamental insights arising from the combination of kinetics, spectroscopy, and multiscale simulations rationalize the improved yield of HMF in water–organic cosolvents. The stability of heterogeneous Lewis acid catalysts under low pH enables tandem Bronsted and Lewis acid-catalyzed reactions in a single pot that overcomes equilibrium limitations and gives a high HMF yield starting from sugar raw materials. Additionally, we provide an overview of multicomponent adsorption of biomass derivatives from solution in microporous materials and discuss how structure–property relations can lead to superior micro- and micromesoporous carbon adsorbents for reactive adsorption toward high HMF yield. Finally, we provide an outlook for the field.

Simultaneous isomerization and reactive extraction of biomass sugars for high yield production of ketose sugars

A desire to achieve one-pot syntheses of value-added products from biomass sugars has led to intense research efforts to convert these sugars with high yields into their ketose forms. Aldose-to-ketose isomerization has an unfavorable equilibrium, and to date, high yield conversion to ketoses in a manner that allows for further conversion economically has yet to be demonstrated. Here, a novel strategy for simultaneous-isomerization and reactive-extraction (SIRE), where the isomerization of aldose sugars and the reactive-extraction of ketoses occur concurrently in the same vessel, is presented. In SIRE, the unfavorable aldose–ketose equilibrium is overcome by selective extraction of ketose from the reaction medium maintained at the optimal pH of the xylose–glucose isomerase (XI) enzyme; the ketose sugar is back-extracted into a low pH strip solution as a pure, concentrated sugar stream. Starting with pure xylose and using Gensweet® for isomerization, best results for xylulose concentration and purification were achieved with an extraction phase of 1-octanol containing naphthalene-2-boronic acid (N2B) and Aliquat® 336. SIRE, followed by a two-stage strip, resulted in a nearly pure xylulose stream at high concentration and yield. Sugar can be concentrated in both the extraction and stripping steps by reducing the volume ratio of the sugar-receiving phase relative to the sugar-donating phase for each step. This result is significant as the separation of isomers is regarded as one of the most challenging and high cost purification processes. When implemented with biomass hydrolyzates, this technology has the potential to provide contaminant-free, concentrated ketose sugar streams without the need for energy-intensive separation and concentration schemes.

Synthesis of Annulated Pyrroles: Condensation of Aldose Sugars, Arylamines, and 1,3-Diones Using TBAB

Readily available tetrabutylammonium bromide (TBAB, 10 mol%), in the molten state, efficiently catalyzes the reaction of a variety of in situ generated enamines, from arylamines and 1,3-ketones, with aldose sugars under solvent-free conditions. The reaction proceeds rapidly and affords the corresponding protected annulated pyrrole derivatives in good to high yields (55-78%) after acetylation. The present methodology offers advantages such as excellent yields, a simple procedure, shorter reaction times, and milder conditions.

The Lighter Side of a Sweet Reaction

The unique advantage of neutrons as biological probes is the ability to visualize hydrogen atoms in macromolecules. In this issue, Kovalevsky et al. (2010) solved an ensemble of xylose isomerase structures by neutron crystallography, and the determination of hydrogen atom rearrangements during the catalytic cycle provides insight into the enzyme's mechanism.

The Novel Function of Advanced Glycation End Products in Regulation of MMP-9 Production

Advanced glycation end products (AGEs), formed from proteins and peptides by nonenzymatic glycoxidation after contact with aldose sugars, have been implicated in the pathogenesis of age-related cardiac and vascular dysfunction. Our previous study demonstrated significantly elevated levels of AGE and the receptor for AGE (RAGE) in human abdominal aortic aneurysm (AAA) tissues. Inhibition of AGE signaling by targeted gene deletion of RAGE markedly reduced the development of aneurysm in a mouse model of AAA. We also showed that AGE may stimulate aneurysm formation by promoting metalloproteinase (MMP)-9 expression. In this study, we investigated the molecular mechanism underlying this novel function of AGE. The murine macrophage cell line RAW 264.7 was pretreated with AGE, TGF-β, and MAPK inhibitors. The protein was collected for Western blot analysis. Culture supernatants were collected to determine MMP-9 activity by gelatin zymography. We found that AGE induced the production of MMP-9 in macrophages in a dose-dependent manner. This induction of MMP-9 was markedly diminished by pretreatment with TGF-β. To delineate the underlying molecular mechanism, we showed that AGE increased phosphorylation of p44/42 ERK, p38, JNK, and PI3K in macrophages. Moreover, AGE induced active p65 subunit of NF- κB. Inhibition of ERK (UO126) or p38 (SB203580), but not PI3K (LY294002 or wortmannin), blocked AGE-induced MMP-9 expression. In contrast, inhibition of JNK (SP-600125) significantly enhanced the stimulatory effect of AGE on MMP-9. Furthermore, TGF-β suppressed AGE-induced expression of the active p65 subunit of NF-κB. Our data indicate that AGE induces MMP-9 through activation of ERK, p38 mitogen-activated protein and NF-κB, a pathway that is antagonized by TGF-β. This finding in conjunction with previously reported AGE functions in inflammation suggests that anti-AGE therapies could be effective in the prevention of human AAA development and progression.

The Novel Function of Advanced Glycation End Products in Regulation of MMP-9 Production

Introduction: Abdominal aortic aneurysms (AAAs) are a common clinical problem that is in great need of pharmacological treatments. Matrix metalloproteinases (MMP)-9 is considered to be an important mediator for the development of AAAs. Advanced glycation end products (AGEs) are formed from proteins and peptides by non-enzymatic glycoxidation after contact with aldose sugars. The accumulation of AGEs and inflammation ligands has been demonstrated in the pathogenesis of age-related cardiac and vascular dysfunction.

Effect of Nicotine on Advanced Glycation End Product-Induced Immune Response in Human Monocytes

The up-regulation of adhesion molecule expressions on monocytes enhances cell-to-cell interactions with T cells, leading to cytokine production. Advanced glycation end products (AGEs) are modifications of proteins/lipids that become nonenzymatically glycated after contact with aldose sugars. Among various subtypes of AGEs, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) induce the expressions of intercellular adhesion molecule-1, B7.1, B7.2, and CD40 on monocytes, the production of interferon-gamma and tumor necrosis factor-alpha, and the lymphocyte proliferation in human peripheral blood mononuclear cells. Nicotine is reported to inhibit the activation of monocytes via nicotinic acetylcholine receptor alpha7 subunit (alpha7-nAChR). In the present study, we found that nicotine inhibited the actions of AGE-2 and AGE-3. A nonselective and selective alpha7-nAChR antagonist, mecamylamine and alpha-bungarotoxin, reversed the inhibitory effects of nicotine, suggesting the involvement of alpha7-nAChR stimulation. Nicotine induced the expression of cyclooxygenase-2, prostaglandin E(2) (PGE(2)), and cAMP in the presence and absence of AGE-2 and AGE-3. PGE(2) is known to activate the EP(2)/EP(4) receptor, increasing the cAMP level and protein kinase A (PKA) activity. The actions of nicotine were reversed in part by an EP(2)-receptor antagonist, AH6809, an EP(4)-receptor antagonist, AH23848, and a PKA inhibitor, N-[2-(p-bromocinnamyl-amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89). These results indicate that the mechanism of action of nicotine may be partially via endogenous PGE(2) production.

Histamine Inhibits Advanced Glycation End Products-Induced Adhesion Molecule Expression on Human Monocytes

Advanced glycation end products (AGEs) are modifications of proteins/lipids that become nonenzymatically glycated after contact with aldose sugars. Among various subtypes of AGEs, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are suggested to play roles in inflammation in diabetic patients. Because the engagement of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, and CD40 on monocytes with their ligands on T cells plays roles in cytokine production, we examined the effects of AGE-2 and AGE-3 on the expression of adhesion molecules and cytokine production in human peripheral blood mononuclear cells (PBMC) and their modulation by histamine in the present study. AGE-2 and AGE-3 induced the expressions of ICAM-1, B7.1, B7.2, and CD40 on monocytes and the production of interferon-gamma in PBMC. Histamine concentration-dependently inhibited the action of AGE-2 and AGE-3. The effects of histamine were antagonized by an H2 receptor antagonist, famotidine, and mimicked by H2/H4 receptor agonists dimaprit and 4-methylhistamine. Histamine induced cAMP production in the presence and absence of AGE-2 and AGE-3. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89), and mimicked by a dibutyryl cAMP and an adenylate cyclase activator, forskolin. These results as a whole indicated that histamine inhibited the AGE-2- and AGE-3-induced adhesion molecule expression and cytokine production via H2 receptors and the cAMP/PKA pathway.

Three-Component Reaction of Aldose Sugars, Aryl Amines, and 1,3-Diones: A Novel Synthesis of Annulated Pyrroles

Aldose sugars undergo smooth coupling with enamines, generated in situ from aryl amines and 1,3-diketones, in the presence of 10 mol % of InCl3 in water at 80 degrees C to furnish annulated pyrrole derivatives in relatively good to high yields. The use of InCl3, in combination with water, makes this procedure quite simple, more convenient, and environmentally friendly.

Identification in the mouldHypocrea jecorinaof a gene encoding an NADP+: d-xylose dehydrogenase

A gene coding for an NADP+-dependent d-xylose dehydrogenase was identified in the mould Hypocrea jecorina (Trichoderma reesei). It was cloned from cDNA, the active enzyme was expressed in yeast and a histidine-tagged enzyme was purified and characterized. The enzyme had highest activity with d-xylose and significantly smaller activities with other aldose sugars. The enzyme is specific for NADP+. The Km values for d-xylose and NADP+ are 43 mM and 250 μM, respectively. The role of this enzyme in H. jecorina is unclear because in this organism d-xylose is predominantly catabolized through a path with xylitol and d-xylulose as intermediates and the mould is unable to grow on d-xylonic acid.

Variation in the Nature of Organic Acid Secretion and Mineral Phosphate Solubilization by Citrobacter sp. DHRSS in the Presence of Different Sugars

A novel phosphate solubilizing bacterium (PSB) was isolated from the rhizosphere of sugarcane and is capable of utilizing sucrose and rock phosphate as the sole carbon and phosphate source, respectively. This PSB exhibited mineral phosphate solubilizing (MPS) phenotype on sugars such as sucrose and fructose, which are not substrates for enzyme glucose dehydrogenase (GDH), along with GDH substrates, viz., glucose, xylose, and maltose, as carbon sources. PCR amplification of the rRNA gene and sequence analysis identified this bacterium as Citrobacter sp. DHRSS. On sucrose and fructose Citrobacter sp. DHRSS liberated 170 and 100 microM free phosphate from rock phosphate and secreted 49 mM (2.94 g/L) and 35 mM (2.1 g/L) acetic acid, respectively. Growth of Citrobacter sp. DHRSS on sucrose is mediated by an intracellular inducible neutral invertase. Interestingly, in the presence of GDH substrates like glucose and maltose, Citrobacter sp. DHRSS produced approximately 20 mM (4.36 g/L) gluconic acid and phosphate released was 520 and 570 microM, respectively. Citrobacter sp. DHRSS GDH activity was found when grown on GDH and non-GDH substrates, indicating that it is constitutive and could act on a wide range of aldose sugars. This study demonstrates the role of different organic acids in mineral phosphate solubilization by rhizobacteria depending on the nature of the available carbon source.