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Different proton-sugar stoichiometries for the uptake of glucose analogues by Chlorella vulgaris. Evidence for sugar-dependent proton uptake without concomitant sugar uptake by the proton-sugar symport system.

The uptake of hexoses by Chlorella vulgaris is accompanied by the uptake of protons. For 6-deoxyglucose a stoichiometry of one proton taken up per sugar molecule has been measured, whereas for 1-deoxyglucose approximately two protons are taken up per sugar molecule. It was found that in the presence of 1-deoxyglucose a considerable proportion of "carrier" catalyzes the transport of protons without the concomitant transport of sugar. Presumably, the binding of sugar initiates the translocation of the carrier-proton-sugar complex, but whereas 1-deoxyglucose can still dissociate from the complex at the external side of the cytoplasmic membrane, the translocation of the carrier-proton complex continues. This conclusion was reached since (a) the composition of the translocated carrier-proton-sugar complex is the same for both sugar. Its formation is a first order reaction with respect to protons. (b) When 6-deoxyglucose, present inside cells, is exchanged for external sugar, the exchange ratio is two to one when the external sugar is 1-deoxyglucose, two molecules of 6-deoxyglucose are lost for each molecule of 1-deoxyglucose entering. This result indicates that during uptake of 1-deoxyglucose statistically only each second carrier molecule appearing at the internal side of the cytoplasmic membrane is carrying sugar.

Binding Sites↗

Structures of the asparagine-linked sugar chains of human chorionic gonadotropin produced in choriocarcinoma. Appearance of triantennary sugar chains and unique biantennary sugar chains.

Human chorionic gonadotropin (hCG) highly purified from urine of the patient with choriocarcinoma contains four asparagine-linked sugar chains in one molecule. The sugar chains were quantitatively liberated as radioactive oligosaccharides from polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. The structures of these sugar chains were determined by the combination of sequential glycosidase digestion, periodate oxidation, and methylation analysis. As compared with the sugar chains of normal urinary and placental hCG reported previously, they include several prominent structural differences. More than 97% of the sugar chains of choriocarcinoma hCG was free from sialic acid, while the sugar chains of normal hCG were mostly sialylated. Choriocarcinoma hCG contains unusual biantennary complex-type sugar chains in addition to regular tri-, bi-, and monoantennary sugar chains. These sugar chains have two outer chains linked at the C-2 and C-4 positions of the same alpha-mannosyl residue of the trimannosyl core. Since normal hCG does not contain any triantennary sugar chains, occurrence of Gal beta 1 leads to 4GlcNAc beta 1 leads to 4Man alpha 1 leads to group is another characteristic feature of the sugar chains of choriocarcinoma hCG. The evidence that the monoantennary sugar chain of Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc leads to Asn is not found in normal hCG and the sum total of fucosylated sugar chains is 50%, which is twice as much as normal hCG, indicated that fucosylation is also modified in choriocarcinoma tissue.

Adult↗

The effect of the osmolality of sugar-containing media, the type of sugar, and the mass and molar concentration of sugar on the survival of frozen-thawed mouse sperm.

Several factors have contributed to problems in mouse sperm cryopreservation, and we and others have found ways to ameliorate them. These include high sensitivity to several types of mechanical stresses and to oxygen-derived free radicals, low tolerance to osmotic cell volume changes, and rather rigorous requirements for cooling and warming rates. Another important factor is the cryoprotective agent. Mouse sperm are unusual in that our best results have been obtained in media containing the nonpermeating sugar raffinose (18% w/v) and lacking glycerol. This paper deals with questions about the basis of the protective action of sugars, and whether raffinose is unusual or unique in its ability to confer protection. More specifically, we investigated whether protection was more related to the total osmolality of the freezing solution, to the mass concentration of sugar, or to the molarity of the sugar, and we looked to see whether there are effects attributable to specific sugars. To investigate these questions, mouse sperm were frozen at the optimal rate of 25 degrees C/min in solutions prepared with different proportions of three sugars-raffinose, sucrose, and glucose-dissolved in 1/4x PBS. In the first experimental series, the total osmolality and the total sugar molarity were varied from 400 to 700 mOsm and from 300 to 530 mM, respectively, while holding the mass concentration of sugar constant at 18% (w/v). In the second experimental series, the mass concentration of sugars was varied from 10 to 18% while the sugar molarity and solution osmolality remained constant at 300 mM and 420 mOsm, respectively. The results suggest that protection against freezing and thawing depends more on the mass concentration of the sugar than on its molar concentration, a conclusion that has mechanistic implications.

Animals↗

Simultaneous assay of neutral sugars and amino sugars by an automatic sugar analyzer: applications to glycoproteins.

The simultaneous assay of neutral sugars and amino sugars commonly found in glycoproteins is described. The automatic sugar analyzer used for the determination is based on the ion-exchange chromatography of sugar-borate complexes on a strong anion-exchange resin. The sugars are identified with the orcinol/sulfuric acid reagent. While less than 40 nmol of mannose, fucose, galactose, glucose, xylose, or arabinose is sufficient for analysis at least 200 nmol mannosamine, glucosamine, or galactosamine is required; acidic monosaccharides cannot be determined. The technique of sugar analysis is applied to structural studies on natural compounds, e.g. the monosaccharide composition of lichenan and the carbohydrate moiety of the glycoproteins ovomucoid and Collocalia mucoid.

Amino Sugars↗

Sugar-dependent rats show enhanced responding for sugar after abstinence: evidence of a sugar deprivation effect.

Studies have shown that intermittent sugar availability (12 h/day) produces signs of dependence in rats, including escalation of intake, mu-opioid and dopamine receptor changes, behavioral and neurochemical indices of withdrawal, and cross-sensitization with amphetamine. "Deprivation-effect" paradigms, whereby abstinence from a substance results in enhanced intake, are often used to measure "craving" for drugs of abuse, such as alcohol. The present study used operant conditioning to investigate consumption of sugar after abstinence in rats selected for glucose avidity. The experimental group was trained on a fixed ratio (FR-1) schedule for 25% glucose for 30 min/day for 28 days and also had glucose access in the home cages for an additional 11.5 h daily. The control group had only the 30-min/day access to glucose in the operant chambers. Then, both groups were deprived of glucose for 2 weeks. After this period of abstinence, animals were put back in the operant chambers. The experimental group responded significantly more than ever before, and significantly more than the control group. In conclusion, daily 12-h access to sugar, in the paradigm used, can result in an altered neural state that lasts throughout 2 weeks of abstinence, leading to enhanced intake. Together with previous results, this deprivation effect supports the theory that animals may become dependent on sugar under selected dietary circumstances.

Amphetamine-Related Disorders↗

Location of the sugar-binding site of L-arabinose-binding protein. Sugar derivative syntheses, sugar binding specificity, and difference Fourier analyses.

The sugar-binding site of the L-arabinose-binding protein, an essential component of the high affinity L-arabinose uptake system in Escherchia coli, is located deep in a cleft formed by the asymmetric contributions from both of the two similar domains. The site was unambiguously identified with the electron-rich substrate analog 6-bromo-6-deoxy-D-galactose in a difference Fourier analysis. The observation that the original native structure might have been solved with bound L-arabinose necessitated the synthesis of a heavy atom analog, its structure consistent with the known sugar-binding specificity of the protein. Difference Fourier maps (3.5 A) of crystals soaked in 46 mM analog showed a peak 3.5 times background, which is attributed to the -CH2Br moiety of the analog. Superposition of a difference map onto a 2.8-A native electron density map indicated that the difference peak is 6 to 7 A from the reactive single cysteine (Cys-64) and partially coincident with an "extraneous" density found in the native map. This "extraneous" peak was previously attributed to a bound L-arabinose molecule, and its presence accounts for the early failures of difference Fourier analyses of crystals soaked in or co-crystallized with L-arabinose to locate the sugar-binding site.

Arabinose↗

Sugar transport. Properties of mutant bacteria defective in proteins of the phosphoenolpyruvate: sugar phosphotransferase system.

The bacterial phosphotransferase system (PTS) catalyzes the transfer of the phosphoryl group from phosphoenolpyruvate to its sugar substrates, PTS sugars, concomitant with the translocation of these sugars across the bacterial membrane. The phosphorylation of a given sugar requires four proteins, two general proteins, Enzyme I, and the histidine-containing phosphocarrier protein of the PTS (HPr), used for all sugars, and a pair of proteins specific for that sugar, designated an Enzyme II complex. The phosphotransferase system has been implicated in regulating the induction of synthesis of some catabolic enzyme systems required for the utilization of sugars that are not substrates of the phosphotransferase system, and this and the accompanying reports are concerned with this phenomenon in Salmonell typhimurium and Escherichia coli. Mutants defective in Enzyme I (ptsI), HPr (ptsH), and certain Enzymes II were isolated, and their abilities to ferment and grow on a wide range of sugars and other compounds were determined. The mutants showed the expected properties on PTS sugars, but in addition, ptsH and tight ptsI mutants were unable to utilize certain non-PTS sugars, including maltose, melibiose, glycerol, glycerol-P, mannose-6-P, and, in E. coli, lactose. Leaky Enzyme I mutants could utilize these carbohydrates, but were unable to use them in the presence of a PTS sugar such as methyl alpha-D-glucopyranoside. In accord with the results reported by other laboratories, the inability of the mutants to utilize the non-PTS sugars was explained by the fact that these cells could not be normally induced to synthesize the corresponding catabolic enzyme systmes. This phenomenon is designated PTS-mediated repression. PTS-mediated repression was also observed in wild type cells, but by comparing wild type and leaky pts mutants it was shown that the sensitivity to repression by PTS sugars was greatest in mutants containing the lowest levels of Enzyme I or HPr. Furthermore, ptsI mutants containing a second site mutation in a gene for an Enzyme II were not repressed by the sugar substrate of that Enzyme II, although repression by other PTS sugars was not affected. Transport and other studies further indicated that neither appreciable uptake nor metabolism of the PTS sugars was required for these compounds to effect repression. The ptsH mutants showed the same phenotypic properties as the ptsI mutants with some important exceptions. First, they could ferment and grow on a PTS sugar, fructose. Second, after growth on fructose, (and to a lesser extent on glucose or mannose), such mutants were capable of utilizing other PTS sugars for a few generations. Third, growth of the ptsH mutants on fructose relieved PTS-mediated repression; after growth on fructose, but not on lactate, the mutants could grow for several generations on non-PTS sugars. Preliminary experiments indicated that growth on fructose resulted in the formation of one or more proteins that could substitute for HPr in the utilization of both PTS and non-PTS sugars.

Acetylglucosamine↗

Net sugar transport is a multistep process. Evidence for cytosolic sugar binding sites in erythrocytes.

Human erythrocyte net sugar transport is hypothesized to be rate-limited by reduced cytosolic diffusion of sugars and/or by reversible sugar association with intracellular macromolecules [Naftalin, R.J., Smith, P.M., & Roselaar, S.E. (1985) Biochim. Biophys. Acta 820, 235-249]. The present study examines these hypotheses. Protein-mediated 3-O-methylglucose uptake at 4 degrees C by human erythrocytes and by resealed, hypotonically lysed erythrocytes (ghosts) is inhibited by increasing solvent viscosity. Protein-mediated transport and transbilayer diffusion of the slowly transported substrate 6-NBD glucosamine are unaffected by increasing solvent viscosity. These findings suggest that protein-mediated 3-O-methylglucose transport is diffusion-limited in erythrocytes. More detailed analyses of red cell 3-O-methylglucose uptake (at 4 degrees C and at limiting extracellular sugar levels) reveal that net influx is a biexponential process characterized by rapid filling of a small compartment (C1 = 29 +/- 6% total cell volume; k1 = 7.4 +/- 1.7 min-1) and slow filling of a larger compartment (C2 = 71 +/- 6% total cell volume k2 = 0.56 +/- 0.11 min-1). Erythrocyte D-glucose net uptake at 4 degrees C is also a biphasic process. Transmembrane sugar leakage is a monoexponential process indicating that multicomponent, protein-mediated uptake does not result from sugar uptake by two cell populations of differing cellular volume. Sugar exit at limiting 3-O-methylglucose concentrations is described by single exponential kinetics. This demonstrates that multicomponent sugar uptake does not result from influx into two populations of cells with widely different sugar transporter content. We conclude that biexponential sugar uptake results from slow (relative to transport) exchange of sugars between serial, intracellular sugar compartments. Biexponential sugar uptake is observed under equilibrium exchange conditions (intracellular sugar concentration = extracellular sugar concentration) but only at 3-O-methylglucose concentrations of less than 1 mM. Above this sugar concentration, exchange uptake is a monoexponential process. Because diffusion rates are independent of diffusant concentration, this suggests that multicomponent uptake results from high-affinity sugar binding within the cell. The concentration of cytosolic binding sites (30 microM, Kd(app) = 400 microM) was estimated from the equilibrium cellular 3-O-methylglucose space. Biexponential net 3-O-methylglucose uptake is also observed in human erythrocyte ghosts, in control human K562 cells, and in K562 cells induced to synthesize hemoglobin by prolonged exposure to hemin. This demonstrates that neither membrane-bound nor free cytosolic hemoglobin forms the sugar-binding complex.(ABSTRACT TRUNCATED AT 400 WORDS)

3-O-Methylglucose↗

Pomegranate juice sugar fraction reduces macrophage oxidative state, whereas white grape juice sugar fraction increases it.

The antiatherogenic properties of pomegranate juice (PJ) were attributed to its antioxidant potency and to its capacity to decrease macrophage oxidative stress, the hallmark of early atherogeneis. PJ polyphenols and sugar-containing polyphenolic anthocyanins were shown to confer PJ its antioxidant capacity. In the present study, we questioned whether PJ simple or complex sugars contribute to the antioxidative properties of PJ in comparison to white grape juice (WGJ) sugars. Whole PJ decreased cellular peroxide levels in J774A.1 macrophage cell-line by 23% more than PJ polyphenol fraction alone. Thus, we next determined the contribution of the PJ sugar fraction to the decrease in macrophage oxidative state. Increasing concentrations of the PJ sugar fraction resulted in a dose-dependent decrement in macrophage peroxide levels, up to 72%, compared to control cells. On the contrary, incubation of the cells with WGJ sugar fraction at the same concentrations resulted in a dose-dependent increment in peroxide levels by up to 37%. The two sugar fractions from PJ and from WGJ showed opposite effects (antioxidant for PJ and pro-oxidant for WGJ) also in mouse peritoneal macrophages (MPM) from control as well as from streptozotocin-induced diabetic Balb/C mice. PJ sugar consumption by diabetic mice for 10 days resulted in a small but significant decrement in their peritoneal macrophage total peroxide levels and an increment in cellular glutathione content, compared to MPM harvested from control diabetic mice administrated with water. In contrast, WGJ sugar consumption by diabetic mice resulted in a 22% increment in macrophage total peroxide levels and a 45% decrement in cellular glutathione content. Paraoxonase 2 activity in macrophages increases under oxidative stress conditions. Indeed, macrophage paraoxonase 2 activity was decreased after PJ sugars supplementation, but increased after WGJ sugars supplementation. We conclude that PJ sugar fraction, unlike WGJ sugar fraction, decreases macrophage oxidative state under normal and under diabetic conditions. These antioxidant/antiatherogenic effects could be due to the presence of unique complex sugars and/or phenolic sugars in PJ.

Animals↗

The human erythrocyte sugar transporter presents two sugar import sites.

The human erythrocyte sugar transporter presents sugar import (e2) and sugar export (e1) sites simultaneously. This study asks whether the sugar transporter exposes only one or multiple import sites. We approached this question by analysis of cytochalasin B binding to the human erythrocyte sugar export site in the presence of sugars that bind to the sugar import site. Extracellular maltose does not enter human erythrocytes. High concentrations of maltose (1-100 mM) inhibit cytochalasin B binding to human red cells. Low concentrations (25-500 microM) increase the level of erythrocyte cytochalasin B binding. Maltose modulation of cytochalasin B binding is mediated by altered affinity of sugar export sites for cytochalasin B. Similar results are obtained with other cell-impermeant inhibitors of sugar uptake. Extracellular D-glucose (a transported sugar) stimulates cytochalasin B binding at low D-glucose concentrations (10-250 microM), but this effect is lost at higher concentrations. Intracellular D-glucose inhibits cytochalasin B binding. Low concentrations of extracellular maltose and other nontransported inhibitors stimulate 3-O-methylglucose uptake in erythrocytes. Higher sugar concentrations (1-100 mM) inhibit transport. These data support the hypothesis that the erythrocyte sugar transporter presents two sugar import sites and at least one sugar export site. This conclusion is consistent with the proposed oligomeric structure of the sugar transporter, a complex of four GluT1 proteins in which each subunit presents a translocation pathway.

3-O-Methylglucose↗

Content of iron, copper and zinc in white sugar samples from Polish and other European sugar factories.

White sugar is a very pure food product, even though it contains very small, significant amounts of soluble and insoluble impurities. The content of these impurities has nutritional significance and determines the usefulness of sugar for various industrial applications. The aim was to evaluate the content of iron, copper and zinc in samples of white sugar from Polish factories compared with commercial white sugar samples from other European countries. The investigations were conducted on 72 campaign-averaged white sugar samples from 37 different Polish sugar factories from 1996 to 2000 and on 16 commercial white sugar samples from nine European countries. The content of iron, copper and zinc in those sugar samples was determined by means of FAAS both in the sediment and in the solution after filtration on 0.45- micro m filters of sugar water solution. The content of iron, copper and zinc was low (averages 0.29, 0.06 and 0.07 mg x kg(-1), respectively) in all the white sugar samples from Polish sugar factories and other European countries. Iron and copper found in all white sugar samples were mainly in insoluble form - 77 and 69%, respectively. The contents of water-insoluble iron and water-soluble zinc in white sugar increase with a lowering of the quality of sugar evaluated according to the standards of the EU sugar market regime.

Copper↗

Heat protection by sugars and sugar analogues.

We have examined the relative ability of 16 sugars and sugar analogues to reduce cell killing by hyperthermia of 40 min, 45 degrees C. In general, sugars were added to the culture medium 6 h prior to heating at a concentration of 100 mM (400 mosmol). The results show that D-hexoses, L-hexoses, methylated or thiolated sugars and disaccharides significantly protected cells against thermal damage, increasing survival by factors of 10 to 100. The degree of protection varied for specific sugars and could not be predicted on the basis of sugar conformation or the number of hydroxyl groups. Relative heat protection was partially dependent on the survival assay technique (pre- and post-plating); consistently lower cell survival was measured when cells were subcultured after hyperthermia, both in medium-control and sugar-protected cells. However, the time dependence of heat protection appeared independent of pre- and post-plating. Cell survival after heating was not increased by two sugars: (a) D-idose, and (b) 2-deoxy-D-galactose. The latter sugar, curiously, was also a heat protector but only when cells were trypsinized after hyperthermia. Both of these sugars were relatively more toxic at 37 degrees C under identical treatment conditions. The lack of protection by these two sugars is not understood. Another reported non-sugar heat protector, sodium butyrate, was included as an additional control. Heat protection by butyrate was not observed in CHO cells. The accumulation of intracellular free sugar was measured by gas chromatography after incubating cells for 6 h, 37 degrees C with talose, idose, L-galactose or 1-O-methyl-D-glucose. All of these sugars were found in high concentrations inside of cells. The data are consistent with the hypothesis that polyhydroxy compounds must accumulate intracellularly for cellular heat protection.

Animals↗

Loading process of sugars into cabbage petiole and asparagus shoot apex cells by incubation with hypertonic sugar solutions.

The freezing tolerance of cabbage petioles and asparagus shoot apexes was increased by preincubation with 0.8 M sugar solutions. In cabbage petioles with an initial freezing tolerance of -3 degrees C (temperature for 50% cell survival), as determined by both electrolyte leakage and fluorescein diacetate vital staining, the freezing tolerance was increased to -13 degrees C by incubation with sorbitol solutions for 3 h. In meristematic cells of asparagus shoot apexes with an initial freezing tolerance of -7.5 degrees C, as determined by fluorescein diacetate vital staining, the freezing tolerance was increased to -30 degrees C by incubation with 0.8 M sugar solutions for 3 h, although other cells in the shoot apexes were killed by higher freezing temperatures. During incubation of both cabbage petioles and asparagus shoot apexes with sugar solutions, sugars were intracellularly taken up by osmotically induced fluid-phase endocytotic vesicles, as indicated by comovement of Lucifer Yellows carbohydrazide (LYCH) observed with a confocal laser scanning microscope. The amounts of intracellularly taken up sugars increased concomitantly with the formation of endocytotic vesicles depending on the time of incubation in parallel with a gradual increase of freezing tolerance. However, the endocytotic vesicles and their contents were retained not only after prolonged incubation after maximum freezing tolerance had been achieved but also after recovery of these tissue cells to isotonic conditions or after freeze-thawing. These results suggest that although sugars are intracellularly taken up by endocytotic vesicles, they might be sequestered within vesicles, casting doubt on their protective role to the plasma membranes as a main site of freezing injury. The pretreatment with 1 mM p-chloromercuribenzenesulfonic acid (PCMBS), an inhibitor of sugar transport, reduced the amounts of intracellular sugar uptake without affecting the formation of endocytotic vesicles, suggesting that sugars were, at least partly, taken up by sugar transporters. In the pretreatment with PCMBS, the freezing tolerance of incubated tissues with sugar solutions was significantly reduced, although addition of PCMBS per se did not affect survival. These results suggest that sugars taken up by sugar transporters, rather than sugars taken up by endocytotic vesicles, are mainly responsible for the increased freezing tolerance of cabbage petioles and asparagus shoot apexes. Furthermore, we aimed to study the occurrence of fluid-phase endocytosis with LYCH in an isotonic condition. Our results indicated that uptake of LYCH by fluid-phase endocytotic vesicles was not detected microscopically in isotonic condition, although LYCH was spectrofluorimetrically taken up in isotonic condition. Spectrofluorimetric uptake of LYCH was inhibited by addition of probenecid, an anion transport inhibitor. These results suggest that in cabbage petioles and asparagus shoot apexes, LYCH is taken up by anion transport but not by fluid-phase endocytosis in isotonic condition, and uptake of LYCH by fluid-phase endocytosis is restricted to occur only in hypertonic condition.

4-Chloromercuribenzenesulfonate↗

Cell volumes and water contents of frog muscles in solutions of permeant sugars and sugar alcohols.

1. Previous work has suggested that living cells may acquire and then maintain different water contents and hence volume, in solutions containing different concentrations of solutes that are permeant to the cell membrane. Toward better understanding of this phenomenon, two hypotheses were introduced: one hypothesis is based on the membrane-pump theory; another represents an extension of the polarized multilayer theory of cell water, a part of the association-induction (AI) hypothesis. To test the different predictions of these hypotheses, the water contents of frog muscle equilibrated at 25 degrees C in solutions of different concentrations of seven pentoses, seven hexoses, seven dissacharides, two trisaccharides, and six sugar alcohols were determined. 2. The earlier finding of sustained shrinkage of muscle cells in concentrated solutions of permeant solutes was confirmed once more. 3. In equimolal solutions of sugars and sugar alcohols with different steric conformations but the same or closely similar molecular weight(s), muscles had the same or closely similar water content(s). 4. In equimolal solutions of different sugars and sugar alcohols, the equilibrium water contents of the muscles increased with decreasing molecular weights of these solutes. 5. The water contents of muscles, equilibrated in 0.4 M solutions of different sugars and sugar alcohols, are positively correlated with the equilibrium distribution coefficients (or q-values) of the sugar and sugar alcohols in the muscle cell water with a linear correlation coefficient of +0.973. 6. The relationships between the equilibrium water contents of muscles (in solutions containing different concentrations of different sugars and sugar alcohols) and the concentrations of these sugars and sugar alcohols agree in general contours with that predicted by an equation derived on the basis of the polarized multilayer theory of cell water. 7. The experimental findings described above do not agree with the prediction based on the membrane-pump hypothesis; they do agree with all four predictions of the hypothesis based on the polarized multilayer theory of cell water.

Animals↗

An investigation into sugar-containing and sugar-free over-the-counter medicines stocked and recommended by pharmacists in the north western region of England.

Sugar-containing paediatric medicines can contribute to the aetiology of dental caries, and as many are sold over-the-counter (OTC) as are prescribed. This study evaluated a dental health education initiative among pharmacists in the north-west of England in an effort to increase the sales of sugar-free preparations. It also investigated the stocks they held, their recommendations to their customers and their knowledge of, and attitudes to, sugar in medicine as a cause of dental caries. Following a baseline questionnaire, a randomly selected group of pharmacists were sent a dental health education leaflet informing them of the role of sugar-containing medicines in the aetiology of dental caries and a list of sugar-free alternatives which they were asked to stock and recommend. Twelve months later, a second questionnaire was completed by both the test and control groups of pharmacists. The most commonly stocked and recommended OTC paediatric medicines contained sugar. Of the 14 preparations stocked by over 90% of the pharmacists only two were sugar-free. During the year of the study the mean number of sugar-free medicines stocked by the pharmacists in the test group reduced from 7.70 to 7.12 (P < 0.05) and in the control group from 8.39 to 7.45 (P < 0.05). Seventy-seven per cent of the pharmacists thought that sugar in medicines could contribute to caries, but recommended sugar-containing preparations more frequently than sugar-free alternatives. The dental profession needs to actively promote medicines that are sugar-free if there is to be a change from the use of iatrogenic sugar-containing preparations.

Binomial Distribution↗

Effects of specific dietary sugars on the incorporation of 13C label from dietary glucose into neutral sugars of rat intestine and serum glycoproteins.

Although theoretically all glycoprotein sugars can be derived from glucose, it may be hypothesized that specific dietary sugars could be preferential substrates for glycoprotein synthesis. To test this hypothesis, groups of rats received either continuously (continuous-labelling experiment) or for a single nutritional period (pulse-labelling experiment) a 13C-rich diet containing either maize starch or artificially labelled [13C]glucose. Some groups of rats were also provided during a single nutritional period with low amounts (20-200 mg/animal) of low-13C dietary sugars (mannose, galactose, fucose or fructose). If specific dietary sugars were preferentially incorporated into glycoproteins instead of glucose-derived labelled sugars, a decrease would be expected in the intestinal or serum glycoprotein-sugar 13C enrichment monitored by gas chromatography-isotope-ratio mass spectrometry (GC-IRMS). Contrary to this hypothesis the results showed no significant decrease with any of the specific dietary sugars. Furthermore, with dietary low-13C mannose or galactose, a significant increase in 13C enrichment of glycoprotein-sugars was observed compared with some other nutritional groups. Moreover, in the pulse-labelling experiment, dietary mannose and galactose induced similar patterns of 13C enrichment in intestinal and serum glycoprotein-sugars. Therefore, although specific dietary sugars do not appear to be preferential substrates for glycosylation under conditions and doses relevant to current concepts of nutrition, regulatory roles of some specific dietary sugars in relation to glycoprotein-sugar metabolism might be hypothesized. These findings could lead to similar studies using stable-isotope methodology in man which could have practical consequences, especially in parenteral nutrition where glucose is the only sugar provided to the metabolism.

Animals↗

Glycation mediated lens crystallin aggregation and cross-linking by various sugars and sugar phosphates in vitro.

Glycation of lens crystallins results in protein conformational changes, oxidation, browning and aggregation. Though glucose is the major sugar, other sugars and sugar phosphates generated as intermediates of metabolic pathways are present in the lens, albeit at low concentrations. In this study we incubated bovine lens soluble fraction with various sugars and sugar phosphates (5mM for 10 days). The reactivity was in the order trioses > tetroses > pentoses > hexoses. High molecular weight (HMW) aggregates were also formed at a comparable rate. Increased levels of fluorescence were associated with the HMW aggregates with fast reacting sugars. The phosphorylated derivatives were only slightly more reactive than their respective sugars. Interestingly, fructose-1,6-diphosphate was more reactive and cross-linked more readily than fructose-6-phosphate. Gel electrophoresis under reducing and nonreducing conditions showed formation of disulfide linked protein aggregates with slow reacting sugars such as glucose and non-disulfide covalent linked protein aggregates with fast reacting sugars such as erythrose. In contrast, if 0.1 m DTT was present in erythrose incubations (a fast reacting sugar), the HMW aggregate formation was significantly reduced. In order to show the reactivity among the slow reacting hexoses, we incubated lens proteins with 1 M hexoses for 30 days and the results showed that galactose was more reactive and showed higher cross-linking than fructose and glucose. These results thus indicate that relatively low levels of some sugars and sugar phosphates in the lens could be compensated by enhanced lens protein cross-linking and the combined effect could be rather significant with respect to cataractogenesis.

Animals↗