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Cancer cells increase their metabolic activity by enhancing glucose uptake through overexpression of hexose transporters (Gluts). Gluts also have the capacity to transport other molecules besides glucose, including fructose, mannose, and dehydroascorbic acid (DHA), the oxidized form of vitamin C. The majority of research studies in this field have focused on the role of glucose transport and metabolism in cancer, leaving a substantial gap in our knowledge of the contribution of other hexoses and DHA in cancer biology. Here, we summarize the most recent advances in understanding the role that the multifunctional transport capacity of Gluts plays in biological and clinical aspects of cancer, and how these characteristics can be exploited in the search for novel diagnostic and therapeutic strategies.

Pentose and hexose sugars are abundant constituents of waste biomass, making them sustainable, chiral building blocks for organic synthesis. The demand for chiral saturated heterocyclic rings from the pharmaceutical industry is increasing as they provide well-defined three-dimensional frameworks that show increased metabolic resistance. Through the formation of thioacetals, sugars may be manipulated in their straight-chain form and dehydrated selectively under basic conditions at C-2. This approach was applied to an array of sugars and extended to the production of useful chiral THFs via further selective dehydration reactions.

Aim: the present study was carried out to compare the glycoproteins in normal individuals and in patients with hypothyroidism and hyperthyroidism. Materials and Methods: This study was carried out at Meenakshi Medical College & Research Institute on total 90 individuals, 30 hypothyroid patients, 30 hyperthyroid patients and 30 normal individuals were taken as controls. Each group consisted of both sexes and the participants were between the ages of 25 to 50 years. Various parameters like protein bound fucose, hexose, hexosamine, sialic acid and thyroid function test which include ft3, ft4 and TSH were measured in all the 90 individuals. The data was collected and analyzed. Result: Potein bound hexose, sialic acid, fucose and hexosamine decreased in hypothyroid patients when compared to normal individuals, whereas in patients with hyperthyroidism only protein bound hexose and fucose levels increased significantly whereas sialic acid, hexose were decreased when compared to normal individuals. Conclusion: Serum Glycoproteins can be additional markers to ft3, ft4 and TSH and aid in diagnosis and management of thyroid disorders. Keywords: Glycoproteins, Thyroid function test, Hyperthyroidism, Hypothyroidism.

—The investigation of the mechanisms of cytosolic protein degradation is of great fundamental and applied importance. The decrease in the specific activity of formaldehyde dehydrogenase (Fldh1) and formate dehydrogenase (Fdh1) in the wild type strain GS200, the strain with the deletion of the GSS1 hexose sensor gene, and the strain that is defective in autophagy pathway SMD1163 of K. phaffii during short-term and long-term induction with methanol, with or without the addition of the MG132 (proteasome degradation inhibitor), was investigated. It was shown that the duration of cell incubation on methanol had no particular effect on the inactivation of enzymes. The effect of the proteasome inhibitor MG132 was insignificant. Catabolic inactivation of cytosolic and peroxisomal enzymes was damaged in the gss1Δ mutant since glucose signaling was impaired. Fldh1 and Fdh1 are probably degraded via the vacuolar pathway regardless of the duration of methanol induction.

The acidic catalysts play pivotal roles in the dehydration of hexose into 5-hydroxymethylfurfural (HMF). However, these acidic catalysts were usually exogenously added or self-made, which increase ...

Pollen tubes require a high amount of sugars to sustain high growth rate. Sucrose, the main transport form of sugars, can serve as energy supply and as signaling molecules for pollen tube growth. We report the functional characterization of CsHT11, which is a sugar transporter protein/hexose transport protein (STP/HT). CsHT11 shares high homology with the characterized cucumber hexose transporter CsHT1, a pollen-specific gene. Analysis of CsHT11 mRNA and CsHT11 promoter-reporter gene studies revealed CsHT11 specifically expressed in pollen and pollen tubes. Subcellular localization indicated that CsHT11 is a plasma membrane transporter. Heterologous expression in yeast suggests that CsHT11 is an energy-dependent hexose/H+ symporter, with a wide variety of substrate specificity, including glucose, fructose, galactose, and mannose. In vitro pollen germination of different sugars shows that the expression of CsHT11 is significantly increased with higher sucrose content, but not with higher glucose or fructose content, thereby implying that CsHT11 may be involved in sucrose signal transduction. Thus, CsHT11 might have an essential effect on pollen development and pollen tube growth in cucumber.

Rapid pollen tube growth requires uptake of Suc or its hydrolytic products, hexoses, from the apoplast of surrounding tissues in the style. Due to species-specific sugar requirements, reliance of pollen germination and tube growth on cell wall invertase and Suc or hexose transporters varies between species, but it is not known if plants have a sugar transporter that mediates the uptake of both hexose and Suc for pollen tube growth. Here, we show that a sugar transporter protein in apple (Malus domestica), MdSTP13a, takes up both hexose and Suc when expressed in yeast, and is essential for pollen tube growth on Glc and Suc but not on maltose. MdSTP13a-mediated direct uptake of Suc is primarily responsible for apple pollen tube growth on Suc medium. Sorbitol, a major photosynthate and transport carbohydrate in apple, modulates pollen tube growth via the MYB transcription factor MdMYB39L, which binds to the promoter of MdSTP13a to activate its expression. Antisense repression of MdSTP13a blocks sorbitol-modulated pollen tube growth. These findings demonstrate that MdSTP13a takes up both hexose and Suc for sorbitol-modulated pollen tube growth in apple, revealing a situation where acquisition of sugars for pollen tube growth is regulated by a sugar alcohol.

Nostoc microscopicum an effective extracellular polymers (EPs) synthesizer among cyanobacteria was isolated, and its elementary morphological features were defined with the aid of light microscope and CLSM. Bioseparation of EPs from 44 days-aged culture gave 0.90 g/L of the dry powdered extract. Chemical quantification of EPs showed the presence of 550 mg/g of carbohydrate and 395 mg/g of protein. HPLC results depicted the presence of mannose (monomer sugar), fucose (hexose deoxy sugar), mannitol (sugar alcohol) and N- acetylglucosamine (glycoprotein) in the EPs. The vibration-based spectrum produced by FT-IR proves the β-Sheet structure of EPs glycoprotein and the size as 45 kDa by performing SDS-PAGE. Bactericidal activity evaluation of EPs on Pseudomonas aeruginosa and Staphylococcus aureus co-expressed the MIC value as 125 μg/mL, while zone of inhibition was 12 mm for Gram-negative and 8 mm for Gram-positive bacteria. Biofilm inhibition assay was effective in 1.0 mg/mL concentration of EPs in both bacterial strains with a mean rate of 60 percentages which was further confirmed using confocal laser scanning microscopic imaging. This natural polymeric extract of Nostoc microscopicum indicates its possible applications in bactericidal and biofilm inhibition.

High glucose and fructose intake have been proven to display pro-inflammatory roles during the progression of inflammatory diseases. However, mannose has been shown to be a special type of hexose that has immune regulatory functions. In this review, we trace the discovery process of the regulatory functions of mannose and summarize some past and recent studies showing the therapeutic functions of mannose in inflammatory diseases. We conclude that treatment with mannose can suppress inflammation by inducing regulatory T cells, suppressing effector T cells and inflammatory macrophages, and increasing anti-inflammatory gut microbiome. By summarizing all the important findings, we highlight that mannose treatment is a safe and promising novel strategy to suppress inflammatory diseases, including autoimmune disease and allergic disease.

AMPK/SNF1 is the master regulator of energy homeostasis in eukaryotic cells and has a key role in glucose de-repression. If glucose becomes depleted, Snf1 is phosphorylated and activated. Activation of Snf1 is required but is not sufficient for mediating glucose de-repression indicating a second glucose-regulated step that adjusts the Snf1 pathway. To elucidate this regulation, we further explore the spatial dynamics of Snf1 and Mig1 and how they are controlled by concentrations of hexose sugars. We utilize fluorescence recovery after photobleaching (FRAP) to study the movement of Snf1 and how it responds to external glucose concentrations. We show that the Snf1 pathway reacts both to the presence and to the absolute concentration of glucose. Furthermore, we identify a negative feedback loop regulating Snf1 activity. We also show that Mig1 localization correlates with the Snf1 phosphorylation pattern and not with the Mig1 phosphorylation pattern, suggesting that inactivation of Snf1 has a more pronounced effect on the localization of Mig1 than on the phosphorylation of Mig1. Our data offer insight into the true complexity of regulation of this central signaling pathway by one signal (glucose depletion) interpreted by the cell in different ways.

Insufficient delivery of oligonucleotides to muscle and heart remains a barrier for clinical implementation of antisense oligonucleotide (AO)-mediated exon-skipping therapeutics in Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by frame-disrupting mutations in the DMD gene. We previously demonstrated that hexose, particularly an equal mix of glucose:fructose (GF), significantly enhanced oligonucleotide delivery and exon-skipping activity in peripheral muscles of mdx mice; however, its efficacy in the heart remains limited. Here we show that co-administration of GF with peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO, namely, BMSP-PMO) induced an approximately 2-fold higher level of dystrophin expression in cardiac muscles of adult mdx mice compared to BMSP-PMO in saline at a single injection of 20 mg/kg, resulting in evident phenotypic improvement in dystrophic mdx hearts without any detectable toxicity. Dystrophin expression in peripheral muscles also increased. However, GF failed to potentiate BMSP-PMO efficiency in aged mdx mice. These findings demonstrate that GF is applicable to both PMO and PPMO. Furthermore, GF potentiates oligonucleotide activity in mdx mice in an age-dependent manner, and, thus, it has important implications for its clinical deployment for the treatment of DMD and other muscular disorders. Keywords: hexose, peptide-conjugated morpholino oligomer, Duchenne muscular dystrophy, exon skipping, cardiac functions

Compared with traditional thermal sterilization process, pulsed magnetic field (PMF) is a non-thermal sterilization technology with superior advantages of maintaining the nutrition and flavor of food. But little is known about its antimicrobial mechanism. To explore its antimicrobial mechanism, the variation of cell membrane, intracellular biological macromolecules and respiratory metabolism of E. coli O157: H7 after PMF treatment, were investigated. The results showed that PMF could cause cell membrane damage and increase cell membrane permeability, reducing the content of three intracellular macromolecules (protein, ATP and DNA), as well as exhibiting inhibition for ATPase activity. The inhibition rate and superposition rate test confirmed the pathway that affecting the respiratory metabolism of E. coli O157:H7 treated with PMF was hexose monophophate pathway (HMP), via reducing the activity of key enzyme glucose-6-phosphate dehydrogenase in HMP. Besides, PMF also exhibited superior antibacterial effect on E. coli O157:H7 when it was applied in vegetable juices.

We hypothesized that maternal nutrition during the first 50 d of gestation would influence the abundance of hexose transporters, SLC2A1, SLC2A3, and SLC2A5, and cationic amino acid transporters, SLC7A1 and SLC7A2, in heifer uteroplacental tissues. Angus-cross heifers (n = 43) were estrus synchronized, bred via artificial insemination, and assigned at breeding to 1 of 2 dietary intake groups (CON = 100% of requirements to achieve 0.45 kg/d of BW gain or RES = 60% of CON intake) and ovariohysterectomized on day 16, 34, or 50 of gestation (n = 6 to 9/d) in a completely randomized design with a 2 × 3 factorial arrangement of treatments. Uterine cross-sections were collected from the horn ipsilateral to the corpus luteum, fixed in 10% neutral buffered formalin, sectioned at 5 µm, and stained via immunofluorescence for transporters. For each image, areas of fetal membrane (FM; chorioallantois), luminal epithelium (ENDO), superficial glands (SG), deep glands (DG), and myometrium (MYO) were analyzed separately for relative intensity of fluorescence as an indicator of transporter abundance. Analysis of FM was only conducted for days 34 and 50. No transporters in target areas were influenced by a day × treatment interaction (P ≥ 0.06). In ENDO, all transporters were differentially abundant from days 16 to 50 of gestation (P ≤ 0.04), and SLC7A2 was greater (P = 0.05) for RES vs. CON. In SG, SLC7A1 and SLC7A2 were greater (P ≤ 0.04) at day 34 vs. day 16. In DG, SLC2A3 and SLC7A1 were greater (P ≤ 0.05) for CON vs. RES heifers; furthermore, SLC7A1 was greater (P < 0.01) at day 50 vs. days 16 and 34 of gestation. In MYO, SLC7A1 was greater (P < 0.01) for CON vs. RES and was greater (P = 0.02) at days 34 and 50 vs. day 16. There were no differences in FM (P ≥ 0.06). Analysis of all uterine tissues at day 16 determined that SLC2A1, SLC2A3, and SLC7A2 were all differentially abundant across uterine tissue type (P < 0.01), and SLC7A1 was greater (P = 0.02) for CON vs. RES. Analysis of all uteroplacental tissues at days 34 and 50 demonstrated that all transporters differed (P < 0.01) across uteroplacental tissues, and SLC7A1 was greater (P < 0.01) for CON vs. RES. These data are interpreted to imply that transporters are differentially affected by day of gestation, and that hexose and cationic amino acid transporters are differentially abundant across utero-placental tissue types, and that SLC7A1 is responsive to maternal nutritional treatment.

International audience; LC-HRMS Q-TOF method was used to identify and quantify metabolites ofFoleyola billotiiMaire plant. A series of 15 compounds were tentatively identified: three glucosinolates, 2 aliphatic (progoitrin and gluconapin) and 1 indolic (glucobrassicin); six chlorogenic acids, four coumaroyl quinic acid (CoQA) isomers and two feruloyl quinic acid (FQA) isomers; two diglycosylated flavonols, one quercetin-derived and one kaempferol-derived; three sinapic acid derivatives, sinapoyl threonic acid, hexose sinapate and a third derivative supposedly attributed to a feruloyl quinic acid sinapate; and finally, a glycosylatedtrans-cinnamic acid which could correspond to feruloylthreonic acid (FTA). Glucosinolates content was 55 times higher in cultivated plants; chlorogenic acids and flavonols increased too by 5 and 3.5 times, respectively. In contrast, sinapates decreased by 3 times in cultivated plants, this last result can be explained by reduced UV-B intensity in the north of Algeria. The change inF. billotiicompound profile was more quantitative rather than qualitative.

The conceptuses (embryo/fetus and placental membranes) of pigs require energy to support elongation and implantation, and amounts of glucose and fructose increase in the uterine lumen during the peri-implantation period. Conceptuses from day 16 of pregnancy were incubated with either 14C-glucose or 14C-fructose and amounts of radiolabeled CO2 released from the conceptuses measured to determine rates of oxidation of glucose and fructose. Glucose and fructose both transport into conceptuses, and glucose is preferentially metabolized in the presence of fructose, whereas fructose is actively metabolized in the absence of glucose and to a lesser extent in the presence of glucose. Endometrial and placental expression of glucose transporters SLC2A1, SLC2A2, SCL2A3, and SLC2A4 were determined. SLC2A1 messenger RNA (mRNA) and protein, and SLC2A4 mRNA were abundant in the uterine luminal epithelium of pregnant compared to cycling gilts, and increased in response to progesterone and conceptus-secreted estrogen. SLC2A2 mRNA was expressed weakly by conceptus trophectoderm on day 15 of pregnancy, whereas SLC2A3 mRNA was abundant in trophectoderm/chorion throughout pregnancy. Therefore, glucose can be transported into the uterine lumen by SLC2A1, and then into conceptuses by SLC2A3. On day 60 of gestation, the cell-specific expression of these transporters was more complex, suggesting that glucose and fructose transporters are precisely regulated in a spatial-temporal pattern along the uterine-placental interface of pigs to maximize hexose sugar transport to the pig conceptus/placenta.

The aim of this study was to evaluate the differences in the antioxidant activity and phenolic profile of sunflower (Helianthus annuus L.) extracts obtained from the aerial parts of plants harvested at five growth stages. In vitro assays were used to determine the antioxidant activity, i.e., ABTS&bull, + and DPPH&bull, scavenging activity, the ferric-reducing antioxidant power (FRAP) and the ability to inhibit &beta, carotene&ndash, linoleic acid emulsion oxidation. Phenolic compounds, such as mono- and dicaffeoylquinic acid isomers and caffeic acid hexose, were identified using the LC&ndash, TOF&ndash, MS/MS technique. The predominant compound during the growth cycle of the plant was 3,5-di-O-caffeoylquinic acid, whose content was the highest at the mid-flowering stage. The total phenolic content was also the highest in sunflowers at the mid-flowering stage. The main phenolic compound contents were closely correlated with ABTS&bull, scavenging activity and FRAP. No significant correlation was found between the total phenolic content and the antioxidant activity in the emulsion system. The highest antiradical activity and FRAP were generally determined in older plants (mid-flowering and late flowering stages). In conclusion, the aerial parts of sunflowers, in particular those harvested at the mid-flowering stage, are a good plant material from which to obtain phenolic compound extracts, albeit mainly of one class (esters of caffeic acid and quinic acid), with high antioxidant activity.

5-Ethoxymethylfurfural, one of the furan derivatives, is regarded as a promising biofuel and an excellent additive for diesel because of its high-energy density (8.7 kWh/L). Several methods have been developed for the synthesis of 5-ethoxymethylfurfural with various acidic catalysts. It is much more attractive to synthesize 5-ethoxymethylfurfural by using renewable carbohydrates as the starting material. Although a significant amount of research has been performed over the past decade, low production selectivity is limited to its utilization for fuels on a commercial scale. To address these drawbacks, this review focuses on findings using synthesis paths: (1) nucleophilic substitution of 5-chloromethylfurfural with ethanol; (2) etherification of 5-hydroxymethylfurfural with ethanol in the presence of acid catalysts; (3) synthesis from hexose in ethanol through one-pot reaction, which integrates the dehydration of hexose into 5-hydroxymethylfurfural followed by etherification of 5-hydroxymethylfurfural into 5-ethoxymethylfurfural; and (4) efficient production of 5-ethoxymethylfurfural from hexose-based carbohydrates catalyzed by two combined catalyst systems.

Background: Cadmium (Cd) pollution is of serious concern due to its toxic effects in both humans and animals. The study investigates the protective effect of Tinospora cordifolia stem methanolic extract (TCME) on Cd induced hepatotoxicity. Objective(s): The objective of the study was to explore the hepatoprotective effects of T. cordifolia extract. Materials and methods: Rats were administered orally with Cd (5 mg/kg) and TCME (100 mg/kg) for 28 days. At the end of the treatment period, serum and liver tissues homogenates were subjected to biochemical analysis. Results: Cd treated rats showed increased activities of the serum marker enzymes of liver damage such as AST and ALT along with increased levels of LPO and protein carbonyl content in liver tissues. Cd treatment also leads to decreased activities of endogenous antioxidants (SOD, CAT, GSH, GPx and GST), membrane ATPases (Na+K+ATPase, Ca2+ATPase and Mg2+K+ATPase) and the tissue glycoprotein levels (hexose, fucose, hexosamine and sialic acid). Histological analysis revealed vacuolar degeneration of hepatocytes with focal necrosis upon Cd administration. TCME co-treatment restored the biochemical and histological alterations caused by Cd intoxication to near normal levels. Conclusion: The results of the present investigation reveal the hepatoprotective nature of T. cordifolia against Cd induced hepatotoxicity. Keywords: Cadmium, Oxidative stress, Tinospora cordifolia, Hepatotoxicity, Antioxidant

This study hypothesized to evaluate the effect of betanin, a chromoalkaloid on plasma and altered tissues glycoprotein components in streptozotocin-nicotinamide-induced diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin (45 mg/kg b.w.) dissolved in 0.1 M citrate buffer (pH 4.5) 15 min after the i.p. administration of nicotinamide (110 mg/kg b.w.). Experimental rats were administered betanin at the dose of 20 mg/kg b.w. and glibenclamide (600 µg/kg b.w.) once a day for 30 days. Diabetic rats revealed significant (p < 0.05) increase in the levels of glucose, HbA1C, hexose, hexosamine, sialic acid and fucose in the plasma; decrease in the levels of plasma insulin, Hb and sialic acid in the liver and kidney; significant (p < 0.05) increase in hexose, hexosamine and fucose in the liver and kidney. Moreover, periodic acid-Schiff staining of tissues revealed positive-stain accumulation in diabetic rats. On co-supplementation of betanin and glibenclamide to diabetic rats for the period of 30 days brought back the levels of plasma and tissues glycoprotein components. Based on the present study, we propose that betanin possesses significant protective effect on glycoprotein components in plasma and tissue of diabetic rats.

Objective Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). Methods To examine the relative abundance of glucose and other metabolites in the brain, mouse brain sections were subjected to imaging mass spectrometry at a resolution of 100 μm. This was correlated with immunohistochemistry, qPCR, western blotting and enzyme assays of dissected brain regions to determine the relative contributions of the glycolytic and pentose phosphate pathways to regional glucose metabolism. Results In brain, there are significant regional differences in glucose metabolism, with low levels of hexose bisphosphate (a glycolytic intermediate) and high levels of the pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolite hexose phosphate in thalamus compared to cortex. The ratio of ATP to ADP is significantly higher in white matter tracts, such as corpus callosum, compared to less myelinated areas. While the brain is able to maintain normal ratios of hexose phosphate, hexose bisphosphate, ATP, and ADP during fasting, fasting causes a large increase in cortical and hippocampal lactate. Conclusion These data demonstrate the importance of direct measurement of metabolic intermediates to determine regional differences in brain glucose metabolism and illustrate the strength of imaging mass spectrometry for investigating the impact of changing metabolic states on brain function at a regional level with high resolution., Highlights • Utilization of glucose for glycolysis or the pentose phosphate pathway (PPP) is region-specific. • IMS allows simultaneous measurement of glucose metabolites across brain regions. • PPP is high in thalamus, while glycolysis predominates in cortex and amygdala. • Fasting induces changes in lactate distribution but not glucose metabolites or ATP.

It is of great economic interest to produce succinate from low-grade carbon sources, which can enhance the competitiveness of the biological route. In this study, succinate producer Escherichia coli CT550/pHL413KF1 was further engineered to efficiently use the mixed sugars from non-food based soybean hydrolysate to produce succinate under anaerobic conditions. Since many common E. coli strains fail to use galactose anaerobically even if they can use it aerobically, the glucose, and galactose related sugar transporters were deactivated individually and evaluated. The PTS system was found to be important for utilization of mixed sugars, and galactose uptake was activated by deactivating ptsG. In the ptsG- strain, glucose, and galactose were used simultaneously. Glucose was assimilated mainly through the mannose PTS system while galactose was transferred mainly through GalP in a ptsG- strain. A new succinate producing strain, FZ591C which can efficiently produce succinate from the mixed sugars present in soybean hydrolysate was constructed by integration of the high succinate yield producing module and the galactose utilization module into the chromosome of the CT550 ptsG- strain. The succinate yield reached 1.64 mol/mol hexose consumed (95% of maximum theoretical yield) when a mixed sugars feedstock was used as a carbon source. Based on the three monitored sugars, a nominal succinate yield of 1.95 mol/mol was observed as the strain can apparently also use some other minor sugars in the hydrolysate. In this study, we demonstrate that FZ591C can use soybean hydrolysate as an inexpensive carbon source for high yield succinate production under anaerobic conditions, giving it the potential for industrial application.

AIM To study complete dose-dependent effects of obestatin on lipolytic and glucose transport activities in human adipocyte preparations highly responsive to insulin. METHODS Adipocytes were prepared by liberase digestion from subcutaneous abdominal adipose tissue obtained from overweight subjects undergoing plastic surgery. The index of lipolytic activity was the glycerol released in the incubation medium, while glucose transport was assessed by [3H]-2-deoxyglucose uptake assay. RESULTS When tested from 0.1 nmol/L to 1 μmol/L, obestatin did not stimulate glycerol release; it did not inhibit the lipolytic effect of isoprenaline and did not alter the insulin antilipolytic effect. Obestatin hardly activated glucose transport at 1 μmol/L only. Moreover, the obestatin stimulation effect was clearly lower than the threefold increase induced by insulin 100 nmol/L. CONCLUSION Low doses of obestatin cannot directly influence lipolysis and glucose uptake in human fat cells.

Mice subjected to cold or caloric deprivation can reduce body temperature and metabolic rate and enter a state of torpor. Here we show that administration of pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with diet-induced or genetic obesity. This is associated with marked hypothermia, decreased activity, and decreased metabolic rate. The drop in body temperature correlates with the degree of obesity and is blunted by housing mice at thermoneutrality. Induction of torpor by pyruvate in obese mice relies on adenosine signaling and is accompanied by changes in brain levels of hexose bisphosphate and GABA as detected by mass spectroscopy-based imaging. Pyruvate does not induce torpor in lean mice but results in the activation of brown adipose tissue (BAT) with an increase in the level of uncoupling protein-1 (UCP1). Denervation of BAT in lean mice blocks this increase in UCP1 and allows the pyruvate-induced torpor phenotype. Thus, pyruvate administration induces torpor in obese mice by pathways involving adenosine and GABA signaling and a failure of normal activation of BAT.

Considering the importance of bacterial glycoconjugates on virulence and host mimicry, there is a need to better understand the biosynthetic pathways of these unusual sugars to identify critical targets involved in bacterial pathogenesis. In this report, we describe the cloning, overexpression, purification, and biochemical characterization of the four central enzymes in the biosynthesis pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose, WekG, WekE, WekF, and WekD. Product peaks from enzyme-substrate reactions were detected by using a combination of capillary electrophoresis (CE) and electrospray ionization-mass spectrometry (ESI-MS). Putative enzyme assignments were provided by protein sequence analysis. Combined with the mass spectrometric characterization of pathway intermediates, we propose a biosynthetic pathway for UDP-2-acetamido-4-formamido-2,4,6-trideoxy-hexose. This process involves C-4, C-6 dehydration, C-4 amination, and formylation. CID-ESI-MSn result confirmed that the final product is a 4 formamido derivative too rather than the 3 formamido derivatives as reported earlier.

Adrenoleukodystrophy (X-ALD) is an X-linked genetic disorder caused by mutation of the ATP-binding cassette subfamily D member 1 gene, which encodes the peroxisomal membrane protein, adrenoleukodystrophy protein (ALDP). ALDP is associated with the transport of very-long-chain fatty acids (VLCFAs, carbon chain length ≥ 24) into peroxisomes. Defective ALDP leads to the accumulation of saturated VLCFAs in plasma and tissues, which results in damage to myelin and the adrenal glands. Here, we profiled the glycosphingolipid (GSL) species in fibroblasts from X-ALD patients. Quantitative analysis was performed using liquid chromatography–electrospray ionization–tandem mass spectrometry with a chiral column in multiple reaction monitoring (MRM) mode. MRM transitions were designed to scan for precursor ions of long-chain bases to detect GSLs, neutral loss of hexose to detect hexosylceramide (HexCer), and precursor ions of phosphorylcholine to detect sphingomyelin (SM). Our results reveal that levels of C25 and C26-containing HexCer, Hex2Cer, NeuAc-Hex2Cer, NeuAc-HexNAc-Hex2Cer, Hex3Cer, HexNAc-Hex3Cer, and SM were elevated in fibroblasts from X-ALD patients. In conclusion, we precisely quantified SM and various GSLs in fibroblasts from X-ALD patients and determined structural information of the elevated VLCFA-containing GSLs.

Escherichia coli is an important commercial species used for production of biofuels, biopolymers, organic acids, sugar alcohols, and natural compounds. Processed biomass and agroindustrial byproducts serve as low-cost nutrient sources and contain a variety of hexoses available for bioconversion. However, metabolism of hexose mixtures by E. coli is inefficient due to carbon catabolite repression (CCR), where the transport and catabolic activity of one or more carbon sources is repressed and/or inhibited by the transport and catabolism of another carbon source. In this work, we developed a microconsortium of different E. coli strains, each engineered to preferentially catabolize a different hexose – glucose, galactose, or mannose. We modified the specificity and preference of carbon source using a combination of rational strain design and adaptive evolution. The modifications ultimately resulted in strains that preferentially catabolized their specified sugar. Finally, comparative analysis in galactose- and mannose-rich sugar mixtures revealed that the consortium grew faster and to higher cell densities compared to the wild-type strain. This article is protected by copyright. All rights reserved

Substantial amounts of fructose are present in our diet. Unlike glucose, this hexose cannot be metabolized by most cells and has first to be converted into glucose, lactate or fatty acids by enterocytes, hepatocytes and kidney proximal tubule cells, which all express specific fructose-metabolizing enzymes. This particular metabolism may then be detrimental in resting, sedentary subjects; however, this may also present some advantages for athletes. First, since fructose and glucose are absorbed through distinct, saturable gut transporters, co-ingestion of glucose and fructose may increase total carbohydrate absorption and oxidation. Second, fructose is largely metabolized into glucose and lactate, resulting in a net local lactate release from splanchnic organs (mostly the liver). This 'reverse Cori cycle' may be advantageous by providing lactate as an additional energy substrate to the working muscle. Following exercise, co-ingestion of glucose and fructose mutually enhance their own absorption and storage.

Context: Olive oil is the major source of tyrosol which is a natural phenolic antioxidant. Olive oil constitutes a major component of the Mediterranean diet that is linked to a reduced incidence of chronic diseases. Objective: This study evaluates the effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats. Materials and methods: Diabetes mellitus was induced in male Wistar rats by streptozotocin (40 mg/kg body weight). These rats were administered tyrosol (20 mg/kg body weight) and glibenclamide (600 μg/kg body weight) orally daily for 45 days. Plasma glucose, plasma insulin, glycoprotein components such as hexose, hexosamine, sialic acid and fucose in the plasma, liver and kidney, and histopathogy of tissues were analyzed. Results: Diabetic rats revealed significant (p

Although the Plasmodium falciparum hexose transporter PfHT has emerged as a promising target for anti-malarial therapy, previously identified small-molecule inhibitors have lacked promising drug-like structural features necessary for development as clinical therapeutics. Taking advantage of emerging insight into structure/function relationships in homologous facilitative hexose transporters and our novel high throughput screening platform, we investigated the ability of compounds satisfying Lipinksi rules for drug likeness to directly interact and inhibit PfHT. The Maybridge HitFinder chemical library was interrogated by searching for compounds that reduce intracellular glucose by >40% at 10 μM. Testing of initial hits via measurement of 2-deoxyglucose (2-DG) uptake in PfHT over-expressing cell lines identified 6 structurally unique glucose transport inhibitors. WU-1 (3-(2,6-dichlorophenyl)-5-methyl-N-[2-(4-methylbenzenesulfonyl)ethyl]-1,2-oxazole-4-carboxamide) blocked 2-DG uptake (IC50 = 5.8 ± 0.6 μM) with minimal effect on the human orthologue class I (GLUTs 1-4), class II (GLUT8) and class III (GLUT5) facilitative glucose transporters. WU-1 showed comparable potency in blocking 2-DG uptake in freed parasites and inhibiting parasite growth, with an IC50 of 6.1 ± 0.8 μM and EC50 of 5.5 ± 0.6 μM, respectively. WU-1 also directly competed for N-[2-[2-[2-[(N-biotinylcaproylamino)ethoxy)ethoxyl]-4-[2-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-1,3-bis(mannopyranosyl-4-yloxy)-2-propylamine (ATB-BMPA) binding and inhibited the transport of D-glucose with an IC50 of 5.9 ± 0.8 μM in liposomes containing purified PfHT. Kinetic analysis revealed that WU-1 acts as a non-competitive inhibitor of zero-trans D-fructose uptake. Decreased potency for WU-1 and the known endofacial ligand cytochalasin B was observed when PfHT was engineered to contain an N-terminal FLAG tag. This modification resulted in a concomitant increase in affinity for 4,6-O-ethylidene-α-D-glucose, an exofacially directed transport antagonist, but did not alter the Km for 2-DG. Taken together, these data are consistent with a model in which WU-1 binds preferentially to the transporter in an inward open conformation and support the feasibility of developing potent and selective PfHT antagonists as a novel class of anti-malarial drugs.

Background l-Fucose (Fuc), a six-deoxy hexose monosaccharide, is present endogenously in humans and animals and has a wide range of biological functions. In the present study, we aimed to examine the effect of Fuc on obesity and hepatic steatosis in mice fed a high-fat diet (HFD). Methods C57BL/6 mice were fed a normal chow (NC) or HFD for 18 weeks to induce obesity and fatty liver. Fuc was administered intragastrically from the 8th week to the end of the experiment (18 weeks). Results Metagenomic analysis showed that HFD altered the genomic profile of gut microbiota in the mice; specifically, expression of alpha-l-fucosidase, the gene responsible for Fuc generation, was markedly reduced in the HFD group compared with that in the NC group. Fuc treatment decreased body weight gain, fat accumulation, and hepatic triglyceride elevation in HFD-fed mice. In addition, Fuc decreased the levels of endotoxin-producing bacteria of the Desulfovibrionaceae family and restored HFD-induced enteric dysbiosis at both compositional and functional levels. Conclusion Our findings suggest that Fuc might be a novel strategy to treat HFD-induced obesity and fatty liver.

Colletotrichum higginsianum is an important hemibiotrophic plant pathogen that causes crucifer anthracnose worldwide. To date, some hexose transporters have been identified in fungi. However, the functions of hexose transporters in virulence are not clear in hemibiotrophic phytopathogens. In this study, we identified and characterized a new hexose transporter gene named ChHxt6 from a T-DNA insertion pathogenicity-deficient mutant G256 in C. higginsianum. Expression profiling analysis revealed that six ChHxt genes, ChHxt1 to ChHxt6, exhibited specific expression patterns in different infection phases of C. higginsianum. The ChHxt1 to ChHxt6 were separately deleted using the principle of homologous recombination. ChHxt1 to ChHxt6 deletion mutants grew normally on PDA plates, but only the virulence of ChHxt4 and ChHxt6 deletion mutants was reduced. ChHxt4 was required for fungal infection in both biotrophic and necrotrophic stages, while ChHxt6 was important for formation of necrotrophic hyphae during infection. In addition, ChHxts were functional in uptake of different hexoses, but only ChHxt6-expressing cells could grow on all five hexoses, indicating that the ChHxt6 was a central hexose transporter and crucial for hexose uptake. Site-directed mutation of T169S and P221L positions revealed that these two positions were necessary for hexose transport, whereas only the mutation Thr169 caused reduced virulence and defect in formation of necrotrophic hyphae. Taken together, ChHxt6 might regulate fungal virulence by modulating the utilization of hexose.

The metabolite profiles and antioxidant activity of Dendrobium catenatum Lindley leaf, a new functional ingredient for food product development, were evaluated in samples that had been prepared using various methods, including freeze-drying, hot-air drying, rolling before drying, steaming before drying, steaming and rolling before drying, and drying at 100, 80, and 60 °C. The concentrations of polysaccharides and flavonoids, as well as the antioxidant capacity of each sample, were determined. Furthermore, two nucleosides, four amino acids, one monoaromatic compound, and eight flavonoids were identified in dried leaves using high-performance liquid chromatography–diode array detector–electrospray ionization–multistage mass spectrometry (HPLC-DAD-ESI-MSn) and ultraviolet (UV) spectral analyses. The content of polar compounds such as cytidylic acid, arginine, tyrosine, and hydroxybenzoic acid hexose increased dramatically during hot-air-drying and rolling-before-drying treatments, while flavonol C-glycosides remained stable throughout the various treatments and drying temperatures. Rolling before drying at 100 °C was identified as the most suitable process when manufacturing tea products from D. catenatum leaves. This process resulted in a high-antioxidant-activity and visually appealing tea. This report details a potential strategy that should be applied in the manufacturing processes of high-quality products from D. catenatum leaves.

The present study was undertaken to determine the membrane-stabilizing effect of Bio-tea in the prevention of myocardial injury caused by isoproterenol in rats. The efficiency of Bio-tea pretreatment was compared against black tea pretreatment and the positive control (rats with isoproterenol-induced myocardial infarction) and negative control (normal control rats). For this purpose, biochemical analysis of the in vivo antioxidants (superoxide dismutase, catalase, and reduced glutathione), glycoprotein components (hexose, hexosamine, sialic acid, and fucose), lipids (total, ester and free cholesterol, triglycerides, free fatty acids, and phospholipids), and transmembrane protein activities (Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase) was carried out along with the histological and ultrastructural study of the myocardial tissue. Induction of myocardial infarction using isoproterenol resulted in a significant decrease in tissue antioxidants and an increase in the levels of total, ester and free cholesterol, triglycerides, free fatty acids, and glycoprotein components in plasma and heart. The phospholipid content showed an increase in plasma and a simultaneous decrease in the heart tissue, while the Na+/K+ ATPase activity decreased and Ca2+ ATPase and Mg2+ ATPase activities increased, resulting in destabilization of the membranes. Pretreatment with Bio-tea was able to bring these components to near normal, indicating its reactive-oxygen-species-scavenging, lipid-lowering, membrane-stabilizing and glycoprotein-modulating effects and lending credibility to the regular use of Bio-tea.

Tartary buckwheat bran [ Fagopyrum tartaricum (L.) Gaerth, FG], a major by-product of tartary buckwheat flour production, may serve as a natural source of phenolic compounds with potential antioxidant activity. In this study, the total content of free phenolic compounds was approximately 4-fold larger than that of bound phenolic compounds. Rutin represented the main phenolic compound existing in both free and bound forms. However, caffeic acid hexose, chlorogenic acid, protocatechuic acid and catechin-glucoside were only detected in the bound phenolic fraction. The biological activity tests indicated that the phenolic extracts (free fraction especially) of tartary buckwheat bran might serve as functional compounds that exert antioxidant activities in vitro (oxygen radical antioxidant capacity, ORAC) and ex-vivo (cellular antioxidant activities, CAA), as well as antiproliferative activity against human liver cancer cells (HepG2) in vitro .

Immunospecificity of gram-negative bacteria, including Escherichia coli, is defined by the fine structure of the O-specific polysaccharide chain of the lipopolysaccharide called O-antigen. Structures of the O-antigens have been established for the majority of about 200 known serotypes of E. coli but serotype O162 was among few that have not been studied in this respect yet. In the present work, it was found that bacteria of this serotype produce several O-polysaccharides differing in the main chains composed of N-acetylglucosamine and N-acetylgalactosamine residues as well as in the presence or absence of side-chain 4-deoxy-D-arabino-hexose residues. It was also shown that E. coli O101 produces two linear O-polysaccharides, which are structurally similar to the main chains of E. coli O162, whereas only one of them had been identified in these bacteria earlier.

The objective of this study was to evaluate the effects of reduced glutathione (GSH) supplementation on sperm motility, kinematics, mitochondrial activity and the abundance of sperm hexose transporters during liquid storage of ram semen at 5 ℃. Semen samples from eight rams were pooled and diluted with Tris-egg yolk extender supplemented with 0 (control), 50, 100 and 200 mM GSH, and they were assessed at different processing periods (fresh diluted, stored for 24, 48 and 72 h at 5 ℃). Sperm motility and kinematic parameters were analyzed by computer-assisted sperm analysis (CASA). The hypo-osmotic swelling test (HOST) was used to evaluate the functional integrity of sperm membrane. Eosin-nigrosin and JC-1/PI staining methods were used to assess sperm viability and mitochondrial activity, respectively. The antioxidant status of sperm was examined using biological assays. The changes of sperm hexose transporters (GLUT 3, 5 and 8) were determined using western blot analysis. As compared to the control group, supplementation with 100 and 200 mM GSH improved (P ＜ 0.05) sperm total motility, membrane integrity, motion parameters and mitochondrial activity at 72 h of storage, as well as resulted in the higher sperm antioxidant status after storage from 24 to 72 h. The cooling induced a reduction of GLUT 3 and 8, and GSH treatment at 200 mM retarded the gradual decline of these proteins during the prolonged storage time. Our data suggest that GSH can reduce the decline of semen quality by influencing the antioxidant status and energy metabolism of liquid stored ram spermatozoa. The concentration of 200 mM could be appropriate for ram semen during liquid storage at 5 ℃.

The hexose dehydration product and important renewable feedstock 5-hydroxymethylfurfural can be biocatalytically reduced to 2,5-furandimethanol in 96% yield using coconut (Cocos nucifera L.) water as the biocatalyst at room temperature. The dimer of 5-hydroxymethylfurfural 5,5'-[oxybis(methylene)]bis[2-furaldehyde] can also be reduced to the corresponding diol 5,5'-[oxybis(methylene)]bis-[2-furanmethanol] using coconut (Cocos nucifera L.) water in 95% yield under similar conditions. This biocatalytic system could be reused in four cycles without an appreciable loss in activity.

Hydrogen peroxide is an agent that triggers oxidative stress. Glucose, which is a source of carbon and energy has a regulatory role in many metabolic processes such as growth rate, fermentation capacity and stress response. Schizosaccharomyces pombe has eight hexose transporters with a different affinity for glucose and/or related monosaccharides. In S. pombe, Ght5 is a glucose transporter with high-affinity. We aimed to investigate the effects of H2O2-induced oxidative stress on hexose transporters using glucose repression-resistant mutant strains (ird5 and ird11) of S. pombe. We analyzed the percentage of glucose consumption in S. pombe wild-type and mutant cells under stressed and non-stressed conditions. Then we compared the expression levels of the genes encoding hexose transporters under the same conditions. We confirmed that the glucose consumption efficiencies of the mutants were slower than the wild-type as in earlier study under non-stressed condition. The percentage of glucose consumption reduced by approximately two-fold in ird11 and wild-type, but not change in ird5, under a stressed condition. There is no difference between cells shape and size of S. pombe strains under stressed and non-stressed conditions. Under stress-induced condition, the expression levels of ght3, ght4 genes in ird11 and wild-type, and ght4, ght6 genes in ird5 decreased, but that of ght5 gene remarkably increased in only wild-type. We suggested that oxidative stress caused by H2O2 leads to upregulation of the ght5 gene in S. pombe.

Over recent years, the presence of the sweet taste receptor TIR3 in rodent and human insulin-producing pancreatic islet β-cells was documented. The activation of this receptor by sweet-tasting sucralose mimics several biochemical and functional effects of d-glucose in the β-cells. The present study extends this analogy to the bioelectrical response of β-cells. In this respect, sucralose was inefficient in the absence of d-glucose, but induced on occasion electrical activity in mouse β-cells exposed to low non-stimulatory concentrations of the hexose and potentiated, in a concentration-related manner, the response to stimulatory concentrations of d-glucose. These data indicate that sucralose, acting as an agonist of the TIR3 receptor, exerts an excitatory effect upon pancreatic β-cell bioelectrical activity.

While effects of (a)biotic stress events in the phyllosphere have been studied intensively, possible influences of stress on the arbuscular mycorrhizal hyphosphere has scarcely been investigated. We hypothesised that stress challenge in the phyllosphere could alter primary metabolite profiles of the hyphosphere - the mycelial network connecting plants. Donor plants, connected to receiver plants by mycelial networks, were aphid-challenged during 84 h. Primary metabolite profiles in the hyphosphere were investigated. Gene-expression of plant defence gene PR1 was measured in one of the receiver plants during the challenge. Hexose levels in the hyphosphere increased when donor plants were aphid-challenged. This change in metabolic profile was influenced by leaf sampling from receiver plant. PR1 expression increased in donor plants 48 h after challenge, and consequently 60 h after, in receiver plants. We conclude that aphid infestation of donor plants modified primary carbon metabolism in the hyphosphere. Plant defence response in receiver plants, occurred 12 h after detection of response in the aphid-challenged donor plants. While this work is the first to reveal primary metabolic profiles of the AM hyphosphere, more work is needed to elucidate the possible role of transient changes of hexose metabolism in stress response and signalling processes in the hyphosphere of connected plants.

Diabetes afflicts millions of people worldwide and contributes to elevated risk of cardiovascular disease and stroke. Imaging of hepatic metabolic activity using MRI could prove advantageous for diagnosis, treatment monitoring, etc. With the advent of hyperpolarized (HP) carbon-13 based MRI, rapid imaging of metabolic flux is feasible without the use of ionizing radiation. In this work, we have utilized HP [2-13C]dihydroxyacetone (DHA) to observe hepatic metabolism in real time in a perfused mouse (C57BLKS/J) liver model. We have utilized fatty acids and a 1:10 ratio of pyruvate to lactate in the perfusate to mimic physiological conditions. Figure 1 shows the various metabolites observed following the injection of DHA. Ratios of integrals of three-carbon intermediates and hexose sugars (and phosphates) are used to determine the rate of gluconeogenesis. Hepatic gluconeogenic rates are measured in parallel with gold standard tracer methods, confirming the accuracy of HP imaging. Figure 1: Representative 13C NMR spectrum (sum) of hyperpolarized [2-13C] DHA metabolism in perfused liver at 14.1 T. Spectra were measured without 1H decoupling. Phosphoenolpyruvate (PEP) and glycerol-3-phosphate (G3P) are observed. Note that PEP is normally considered a low concentration metabolites, but it is easily detected here. Disclosure M. Merritt: None. M. Ragavan: None. T. Tsarova: None.

Glucose is a major fuel stimulator of insulin secretion. When the effect of glucose anomers are compared in rat pancreatic islets, insulin secretion induced by the α-anomer is much more than that induced by the β-anomer. Similarly, insulin secretion induced by the α-mannose is higher than that induced by the β-anomer of mannose. It is well known that the α-anomer of hexose is stronger in activating the sweet taste receptor expressed in the taste buds of the tongue. Interestingly, inhibitors of the sweet taste receptor attenuate insulin secretion induced by glucose in pancreatic islets. These results raise an interesting possibility that glucose activates a cell-surface “glucoreceptor,” which resembles the sweet taste receptor in the tongue, and exerts its action in pancreatic β-cells.

The epidemiological studies have shown that antibiotic treatment increases the susceptibility to inflammatory bowel disease development. The disturbance of mucus layer integrity might be one of the possible mechanisms. The aim of the present study was to investigate the effect of antibiotic ceftriaxone treatment on glycoproteins level and its carbohydrate composition in surface mucus layer of rat intestine. The study was done on male Wistar rats (140-160 g). Ceftriaxone (300 mg/kg, i.m.) was administered once a day for 14 days. The surface mucus from terminal ileum and colon were collected on the 15th, 29th and 72nd days of the experiment. Total level of mucus glycoproteins, hexoses, hexosamines, fucose and sialic acids were measured. Ceftriaxone administration did not affect the levels of glycoproteins in rat ileum. In the colon, the levels of glycoprotein were 1.3-fold decreased (Р < 0.05) on the 72nd day of the experiment. These changes were accompanied by the 1.2-fold decrease of hexoses (Р < 0.05) and 3.1-fold (Р < 0.05) decrease of fucose level and 1.5-fold (Р < 0.05) increase of the levels of sialic acids in the surface mucus of the rat colon. Thus, ceftriaxone administration induces the long-term changes in the levels of glycoproteins and carbohydrates composition in the rat colon surface mucus. This could potentially explain the susceptibility to inflammatory bowel disea­ses development.

Melatonin regulates growth in many plants; however, the mechanism remains unclear. In this study, exogenous melatonin feeding resulted in both promotional (≤10 μm) and inhibitory (≥100 μm) effects on maize seedling growth. Initial analyses suggested positive correlations between the amount of melatonin and sucrose synthesis and hydrolysis-related gene expression, enzyme activities, and sucrose metabolites. However, assays of photosynthetic rate, hexokinase (HxK) activity, expression of photosynthetic marker genes, and HxK-related genes showed opposite effects under 10 μm (positive) and 100 μm (negative) melatonin treatments. Similarly, 10 μm melatonin accelerated starch catabolism at night, whereas 100 μm melatonin significantly decreased this process and led to starch accumulation in photosynthetic tissues. Furthermore, expression analysis of genes related to sucrose phloem loading resulted in a slight upregulation of sucrose transporters (SUT1 and SUT2) when seedlings were induced with 10 μm melatonin, while treatment with 100 μm melatonin resulted in significant downregulation of these sucrose transporter genes (SUT1 and SUT2), as well as tie-dyed2 (Tdy2) and sucrose export defective 1. Taken together, these results suggest that low doses of melatonin benefit maize seedling growth by promoting sugar metabolism, photosynthesis, and sucrose phloem loading. Conversely, high doses of melatonin inhibit seedling growth by inducing the excessive accumulation of sucrose, hexose and starch, suppressing photosynthesis and sucrose phloem loading.