Sorbitol dehydrogenase (SDH) catalyzes the interconversion of polyols and ketoses, using zinc and NAD(+) as cofactors. SDH converts sorbitol into fructose and plays an important role in the sorbitol metabolic pathway and in the early embryonic development of many invertebrates. Sorbitol usually accumulates in diapause embryos of insects to protect the embryos from frostbite, which indicates the vital function of SDH in the diapause and diapause-termination stages of embryo development. In this study, a 1311-bp full-length cDNA of As-sdh, including a 28-bp 5' UTR and a 59-bp 3' UTR, was cloned from Artemia sinica. This gene encodes 348 amino-acid proteins. Bioinformatic analysis revealed that this gene is highly conserved in arthropods. The expression patterns of As-sdh were investigated during different stages of embryonic development using real-time PCR and in situ hybridization. As-sdh was expressed at relatively high levels during the 0h embryonic stage, and transcript levels were quite high in 5- and 7-day-old embryos. In situ hybridization analysis showed that As-sdh is expressed in a widely dispersed pattern before incubation but is mainly concentrated on the body surface and the inner wall of the alimentary tract after the nauplius stage. Our results suggest that As-sdh is integral to the process of diapause and diapause termination in A. sinica.

Tup1-Cyc8 (also known as Tup1-Ssn6) is a general transcriptional corepressor. D-Mannitol (mannitol) and D-sorbitol (sorbitol) are the major polyols in nature. Budding yeast Saccharomyces cerevisiae is unable to assimilate mannitol or sorbitol, but acquires the ability to assimilate mannitol due to a spontaneous mutation in TUP1 or CYC8. In this study, we found that spontaneous mutation of TUP1 or CYC8 also permitted assimilation of sorbitol. Some spontaneous nonsense mutations of CYC8 produced a truncated Cyc8 with a C-terminal polyglutamine. The effects were guanidine hydrochloride-sensitive and were dependent on Hsp104, but were complemented by introduction of CYC8, ruling out involvement of a prion. Assimilation of mannitol and sorbitol conferred by other mutations of TUP1 or CYC8 was guanidine hydrochloride-tolerant. It is physiologically reasonable that S. cerevisiae carries this mechanism to acquire the ability to assimilate major polyols in nature.

Gluconobacter oxydans is important in the conversion of D-sorbitol into l-sorbose, which is an essential intermediate for industrial-scale production of vitamin C. In a previous study, the strain G. oxydans WSH-004 could directly produce 2-keto-l-gulonic acid (2-KLG). However, its D-sorbitol tolerance was poor compared with that of other common industrial G. oxydans strains, which grew well in the presence of more than 200 g/L of D-sorbitol. This study aimed to use the microbial microdroplet culture (MMC) system for the adaptive evolution of G. oxydans WSH-004 so as to improve its tolerance to high substrate concentration and high temperature. A series of adaptively evolved strains, G. oxydans MMC1-MMC10, were obtained within 90 days. The results showed that the best strain MMC10 grew in a 300 g/L of D-sorbitol medium at 40°C. The comparative genomic analysis revealed that genetic changes related to increased tolerance were mainly in protein translation genes. Compared with the traditional adaptive evolution method, the application of microdroplet-aided adaptive evolution could improve the efficiency in terms of reducing time and simplifying the procedure for strain evolution. This research indicated that the microdroplet-aided adaptive evolution was an effective tool for improving the phenotypes with undemonstrated genotypes in a short time.

Surfactants, such as glycolipids, are specialty compounds that can be encountered daily in cleaning agents, pharmaceuticals or even in food. Due to their wide range of applications and, more notably, their presence in hygiene products, the demand is continuously increasing worldwide. The established chemical synthesis of glycolipids presents several disadvantages, such as lack of specificity and selectivity. Moreover, the solubility of polyols, such as sugars or sugar alcohols, in organic solvents is rather low. The enzymatic synthesis of these compounds is, however, possible in nearly water-free media using inexpensive and renewable building blocks. Using lipases, ester formation can be achieved under mild conditions. We propose, herein, a "2-in-1" system that overcomes solubility problems, as a Deep Eutectic System (DES) made of sorbitol and choline chloride replaces either a purely organic or aqueous medium. For the first time, 16 commercially available lipase formulations were compared, and the factors affecting the conversion were investigated to optimize this process, owing to a newly developed High-Performance Liquid Chromatography-Evaporative Light Scattering Detector (HPLC-ELSD) method for quantification. Thus, using 50 g/L of lipase formulation Novozym 435® at 50 °C, the optimized synthesis of sorbitol laurate (SL) allowed to achieve 28% molar conversion of 0.5 M of vinyl laurate to its sugar alcohol monoester when the DES contained 5 wt.% water. After 48h, the de novo synthesized glycolipid was separated from the media by liquid-liquid extraction, purified by flash-chromatography and characterized thoroughly by one- and two-dimensional Nuclear Magnetic Resonance (NMR) experiments combined to Mass Spectrometry (MS). In completion, we provide initial proof of scalability for this process. Using a 2.5 L stirred tank reactor (STR) allowed a batch production reaching 25 g/L in a highly viscous two-phase system.

Group B streptococci (GBS) are important neonatal bacterial pathogens that can cause severe invasive disease in the newborn. It is thought that in many cases of invasive neonatal GBS disease, the bacteria ascend the vagina into the uterus and infect the amniotic fluid surrounding the fetus. Important constituents of this environment include the polyols or sugar alcohols of which erythritol, sorbitol and mannitol are examples. The aim of our study was to investigate the effect of polyols on GBS grown in media containing these sugar alcohols.

Through RNA-seq of a mixed fruit sample, fourteen expressed sorbitol dehydrogenase (SDH) genes have been identified from sand pear (Pyrus pyrifolia Nakai). Comparative phylogenetic analysis of these PpySDHs with those from other plants supported the closest relationship of sand pear with Chinese white pear (P. bretschneideri). The expression levels varied greatly among members, and the strongest six (PpySDH2, PpySDH4, PpySDH8, PpySDH12, PpySDH13 and PpySDH14) accounted for 96% of total transcript abundance of PpySDHs. Tissue-specific expression of these six members was observed in nine tissues or organs of sand pear, with the greatest abundance found in functional leaf petioles, followed by the flesh of young fruit. Expression patterns of these six PpySDH genes during fruit development were analyzed in two sand pear cultivars, "Cuiguan" and "Cuiyu". Overall, expression of PpySDHs peaked twice, first at the fruitlet stage and again at or near harvest. The transcript abundance of PpySDHs was higher in "Cuiguan" than in "Cuiyu", accompanied by a higher content of sugars and higher ratio of fructose to sorbitol maintained in the former cultivar at harvest. In conclusion, it was suggested that multiple members of the SDH gene family are possibly involved in sand pear fruit development and sugar accumulation and may affect both the sugar amount and sugar composition.

In children aged ≤4 years, the relative bioavailability of lamivudine oral solution was 37% lower than that of a tablet formulation. An open-label, four-way crossover study was conducted in healthy adults to evaluate the effect of sorbitol, a common liquid excipient, on the pharmacokinetics of lamivudine oral solution (ClinicalTrials.gov identifier, NCT02634073). Sixteen subjects were randomized to one of four sequences consisting of four doses of lamivudine 300 mg (10 mg/mL) alone or with sorbitol 3.2, 10.2, or 13.4 g. Sorbitol 3.2, 10.2, and 13.4 g decreased lamivudine maximum concentration (Cmax ) by 28%, 52%, and 55% and area under the concentration-time curve from time 0 to 24 h (AUC0-24 ) by 20%, 39%, and 44%, respectively. Three subjects (19%) reported five nonserious adverse events (one drug-related). The dose-dependent effects of sorbitol on lamivudine Cmax and AUC0-24 reveal an absorption-based interaction that may decrease lamivudine exposure in patients coadministered sorbitol-containing medicines.

Epidemic obesity and diabetes have led to increased use of low-calorie sweeteners. Although several studies have suggested that consumption of artificial sweeteners, such as aspartame and saccharin, might have negative effects, the potential impacts of natural sweeteners on human health remain largely unknown.

Clinacanthus nutans (Burm. f.) Lindau (C. nutans) has been reported to lower blood glucose level; however, evidence on its efficacy in lowering diabetic complications is limited. The antidiabetic properties of C. nutans aqueous leaf extract on serum metabolic indices, sorbitol production, and aldose reductase enzyme activities in the kidneys, lens, and sciatic nerve of type II diabetic (T2D) rats were evaluated. All rats except normal control rats were fed with a high-fat diet for 8 weeks to induce obesity and subsequently injected with 35 mg/kg streptozotocin to induce type II diabetes. Aqueous leaf extract of C. nutans (100 and 200 mg kg-1 day-1) and quercetin (10 mg kg-1 day-1) were fed orally for 4 weeks. Diabetic rats administered with C. nutans at 100, 200 mg kg-1 day-1 and quercetin had significantly (p < 0.05) lower fasting blood glucose levels post-intervention: 14.2, 14.0, and 19.9 mm, respectively, compared with the untreated group (22.1 mm). Total cholesterol was significantly (p < 0.05) lower in the C. nutans groups in comparison with the diabetic control group. Levels of F2-isoprostane, a marker of oxidative stress, were attenuated in the presence of the extract. Aldose reductase enzyme activity increased by 64, 99, and 0% and total antioxidant activities by 22, 29, and 126%, respectively. Sorbitol levels in the kidney, lens, and nerve were reduced in diabetic rats administered with C. nutans and quercetin group (by 8, 16, and 3%, respectively). The protective effect of the extract to the liver and kidney was confirmed through liver and kidney enzyme markers and histological analyses. The C. nutans has the potential to attenuate T2D-induced metabolic perturbations and complications related to sorbitol accumulation.

The aim of this work was to use glycerol (Gly) and sorbitol (Sor) as plasticizers with oxidized starch potato (OS) to produce biodegradable and environmentally friendly films, and to demonstrate the resulting physicochemical and functional viability without subtracting the organoleptic characteristics of the food. Analyses by water vapor permeability (WVP), attenuated total reflection Fourier transform infrared spectra (ATR-FTIR), scanning electron microscopy (SEM), tensile strength (TS), and transparency (UV) showed that the best film result was with 1.5 g of Gly and 2.0 g of Sor, conferred shine, elasticity 19.42 ± 6.20%, and mechanical support. The starch oxidized to 2.5%, contributing a greater transparency of 0.33 ± 0.12 and solubility of 78.90 ± 0.94%, as well as less permeability to water vapor 6.22 ± 0.38 gmm-2 d-1 kPa-1. The films obtained provide an alternative for use in food due to their organic compounds, excellent visual presentation, and barrier characteristics that maintain their integrity and, therefore, their functionality.

Synthetic regulation of metabolic fluxes has emerged as a common strategy to improve the performance of microbial cell factories. The present regulatory toolboxes predominantly rely on the control and manipulation of carbon pathways. Nitrogen is an essential nutrient that plays a vital role in growth and metabolism. However, the availability of broadly applicable tools based on nitrogen pathways for metabolic regulation remains limited. In this work, we present a novel regulatory system that harnesses signals associated with nitrogen metabolism to redirect excess carbon flux in Bacillus licheniformis. By engineering the native transcription factor GlnR and incorporating a sorbitol-responsive element, we achieved a remarkable 99% inhibition of the expression of the green fluorescent protein reporter gene. Leveraging this system, we identified the optimal redirection point for the overflow carbon flux, resulting in a substantial 79.5% reduction in acetoin accumulation and a 2.6-fold increase in acetate production. This work highlight the significance of nitrogen metabolism in synthetic biology and its valuable contribution to metabolic engineering. Furthermore, our work paves the way for multidimensional metabolic regulation in future synthetic biology endeavors.

The nontoxigenic V. cholerae El Tor strains ferment sorbitol faster than the toxigenic strains, hence fast-fermenting and slow-fermenting strains are defined by sorbitol fermentation test. This test has been used for more than 40 years in cholera surveillance and strain analysis in China. Understanding of the mechanisms of sorbitol metabolism of the toxigenic and nontoxigenic strains may help to explore the genome and metabolism divergence in these strains. Here we used comparative proteomic analysis to find the proteins which may be involved in such metabolic difference.

Diabetes is associated with cardiac metabolic disturbances and increased heart failure risk. Plasma fructose levels are elevated in diabetic patients. A direct role for fructose involvement in diabetic heart pathology has not been investigated. The goals of this study were to clinically evaluate links between myocardial fructose and sorbitol (a polyol pathway fructose precursor) levels with evidence of cardiac dysfunction, and to experimentally assess the cardiomyocyte mechanisms involved in mediating the metabolic effects of elevated fructose. Fructose and sorbitol levels were increased in right atrial appendage tissues of type 2 diabetic patients (2.8- and 1.5-fold increase respectively). Elevated cardiac fructose levels were confirmed in type 2 diabetic rats. Diastolic dysfunction (increased E/e', echocardiography) was significantly correlated with cardiac sorbitol levels. Elevated myocardial mRNA expression of the fructose-specific transporter, Glut5 (43% increase), and the key fructose-metabolizing enzyme, Fructokinase-A (50% increase) was observed in type 2 diabetic rats (Zucker diabetic fatty rat). In neonatal rat ventricular myocytes, fructose increased glycolytic capacity and cytosolic lipid inclusions (28% increase in lipid droplets/cell). This study provides the first evidence that elevated myocardial fructose and sorbitol are associated with diastolic dysfunction in diabetic patients. Experimental evidence suggests that fructose promotes the formation of cardiomyocyte cytosolic lipid inclusions, and may contribute to lipotoxicity in the diabetic heart.

The role of configuration for the affinity labelling of sheep liver sorbitol dehydrogenase by chloro-substituted analogues of 2-bromo-3-(5-imidazolyl)propionate (BrImPpOH) has been studied. A saturation kinetics mechanism applies which includes formation of a reversible complex with the enzyme prior to alkylation of Cys-43. The pseudo first-order inactivation rate-constant, k2, and the dissociation constant for the reversible enzyme-affinity label complex. KEI, were determined at pH 7.4 and 23.5 degrees C. The stereo isomers of each affinity label exhibit different kinetic characteristics but, unlike with horse liver alcohol dehydrogenase, the discrimination between them is not absolute. For the different affinity labels, k2 varies with 2-chloro-3-(5-imidazolyl)methylpropionate (Me-ClImPpOH) > 2-chloro-3-(5-imidazolyl)propionate (ClImPpOH) > 2-chloro-3-(5-imidazolyl)propanol (ClImPOH), consistent with their order of inherent reactivity, and the specificity constant k2/KEI varies with (S)-Me-ClImPpOH > (S)-ClImPpOH > (S)-ClImPpOH > (R)-Me-ClImPpOH > (R)-ClImPpOH. Models of the affinity labels were built into the active site of the predicted subunit structure of the enzyme by using a computer-controlled display system. In each binary complex, the imidazole moiety of the affinity label was liganded to the catalytic zinc atom, and the angle Scys-C alpha-Cl was linear, in accordance with an SN2 mechanism. Both enantiomers of each label could form plausible complexes with the enzyme model, in agreement with the kinetic data. The enantiomeric selectivity, rather than absolute specificity, of the reaction appears due to the anion-binding site in sorbitol dehydrogenase being less developed than in horse liver alcohol dehydrogenase.

To investigate the functions of fructokinase (FRK) in apple (Malus domestica) carbohydrate metabolism, we cloned the coding sequences of MdFRK1 and MdFRK2 from the 'Royal Gala' apple. The results showed that MdFRK2 expression was extremely high in shoot tips and young fruit. Analyses of heterologously expressed proteins revealed that MdFRK2 had a higher affinity for fructose than did MdFRK1, with Km values of 0.1 and 0.62 mM for MdFRK2 and MdFRK1, respectively. The two proteins, however, exhibited similar Vmax values when their activities were significantly inhibited by high concentrations of fructose. MdFRK2 ectopic expression was associated with a general decrease in fructose concentration in transgenic lines. In leaves, increased FRK activity similarly resulted in reduced concentrations of glucose and sucrose but no alterations in sorbitol concentration. When compared with those in the untransformed control, genes involved in sorbitol synthesis (A6PR) and the degradation pathway (SDH1/2) were significantly upregulated in transgenic lines, whereas those involved in sucrose synthesis (SPS1) and other degradation processes (SUSY4, NINV1/2, and HxK2) were downregulated. The activity of enzymes participating in carbohydrate metabolism was proportional to the level of gene expression. However, the growth performance and photosynthetic efficiency did not differ between the transgenic and wild-type plants. These results provide new genetic evidence to support the view that FRK plays roles in regulating sugar and sorbitol metabolism in Rosaceae plants.

Among the preventive and therapeutic options available for dental caries, sugar alcohols (xylitol and sorbitol) have been widely promoted as oral healthcare products due to its perceived anticariogenic effect. However, the therapeutic efficacy of these sugar alcohols against Streptococcus mutans and Candida albicans in a sucrose supplemented environment, as found in disease-prone conditions in the oral cavity, has not been adequately investigated.

Development of specific and selective boron carriers is indispensable for boron neutron capture therapy (BNCT) application. Pentagamaboronon-0 (PGB-0) is a promising candidate as boron carrier compound due to the low but selective cytotoxicity in breast cancer cells. Formerly we reported synthesis of PGB-0 which was ineffective due to its low aqueous solubility. In the present study, we, therefore, introduced the new PGB-0 preparation complexed with sugars to increase its solubility in water. By synthesizing at room temperature and using flash chromatography for the purification, we produced PGB-0 with a yield of 40%. PGB-0 fructose complex (PGB-0-F) and PGB-0 sorbitol complex (PGB-0-Sor) were obtained with smaller particle size compared to PGB-0 suspension in water. Based on the MTT assay, the cytotoxicity of PGB-0-F and PGB-0-Sor were higher than PGB-0 even though still categorized as low cytotoxic agents. In conclusion, we provided PGB-0 with a new method and improved its solubility in water. Further investigations are still needed to develop more efficient PGB-0 as boron carrier for BNCT in various cancers.

Several viscosupplement treatments are available for patients suffering from painful osteoarthritis (OA) of the knee, but few comparative clinical trials have been conducted. The primary objective of the trial was to demonstrate the non-inferiority of Synolis VA (80 mg hyaluronic acid and 160 mg sorbitol) (Group HA1) to Synvisc-One (48 mg hylan GF-20) (Group HA2) at Day 168 in terms of pain relief efficacy in patients with knee OA (Kellgren and Lawrence radiological stage II or III) in whom oral treatment with analgesics, NSAIDs or weak opioids provided insufficient clinical responses or were poorly tolerated.

Sorbitol, a product primarily derived from glucose hydrogenation, has extensive applications in the pharmaceutical, chemical and other industries. Amino styrene-co-maleic anhydride polymer encapsulated on activated carbon (Ru/ASMA@AC) catalysts were developed for efficient glucose hydrogenation and were prepared and confined Ru by coordination with styrene-co-maleic anhydride polymer (ASMA). Through single-factor experiments, optimal conditions were determined to be 2.5 wt.% ruthenium loading and a catalyst usage of 1.5 g, 20% glucose solution at 130 °C, reaction pressure of 4.0 MPa, and a stirring speed of 600 rpm for 3 h. These conditions achieved a high glucose conversion rate of 99.68% and a sorbitol selectivity of 93.04%. Reaction kinetics testing proved that the hydrogenation of glucose catalyzed by Ru/ASMA@AC was a first-order reaction, with a reaction activation energy of 73.04 kJ/mol. Furthermore, the catalytic performance of the Ru/ASMA@AC and Ru/AC catalysts for glucose hydrogenation were compared and characterized by various detection methods. The Ru/ASMA@AC catalyst exhibited excellent stability after five cycles, whereas the traditional Ru/AC catalyst suffered from a 10% decrease in sorbitol yield after three cycles. These results suggest that the Ru/ASMA@AC catalyst is a more promising candidate for high-concentration glucose hydrogenation due to its high catalytic performance and superior stability.

The aim of this study was to determine the effectiveness of prune juice on chronic constipation.