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Frontiers in Nutrition 2023Polydatin is a biologically active compound found in mulberries, grapes, and , and it has uric acid-lowering effects. However, its urate-lowering effects and the...
INTRODUCTION
Polydatin is a biologically active compound found in mulberries, grapes, and , and it has uric acid-lowering effects. However, its urate-lowering effects and the molecular mechanisms underlying its function require further study.
METHODS
In this study, a hyperuricemic rat model was established to assess the effects of polydatin on uric acid levels. The body weight, serum biochemical indicators, and histopathological parameters of the rats were evaluated. A UHPLC-Q-Exactive Orbitrap mass spectrometry-based metabolomics approach was applied to explore the potential mechanisms of action after polydatin treatment.
RESULTS
The results showed a trend of recovery in biochemical indicators after polydatin administration. In addition, polydatin could alleviate damage to the liver and kidneys. Untargeted metabolomics analysis revealed clear differences between hyperuricemic rats and the control group. Fourteen potential biomarkers were identified in the model group using principal component analysis and orthogonal partial least squares discriminant analysis. These differential metabolites are involved in amino acid, lipid, and energy metabolism. Of all the metabolites, the levels of L-phenylalanine, L-leucine, -butanoylcarnitine, and dihydroxyacetone phosphate decreased, and the levels of L-tyrosine, sphinganine, and phytosphingosine significantly increased in hyperuricemic rats. After the administration of polydatin, the 14 differential metabolites could be inverted to varying degrees by regulating the perturbed metabolic pathway.
CONCLUSION
This study has the potential to enhance our understanding of the mechanisms of hyperuricemia and demonstrate that polydatin is a promising potential adjuvant for lowering uric acid levels and alleviating hyperuricemia-related diseases.
PubMed: 37187876
DOI: 10.3389/fnut.2023.1117460 -
Nanomaterials (Basel, Switzerland) Apr 2023Several biochars were synthesized from olive stones and used as supports for TiO, as an active semiconductor, and Pt as a co-catalyst (Pt/TiO-PyCF and Pt/TiO-AC). A...
Several biochars were synthesized from olive stones and used as supports for TiO, as an active semiconductor, and Pt as a co-catalyst (Pt/TiO-PyCF and Pt/TiO-AC). A third carbon-supported photocatalyst was prepared from commercial mesoporous carbon (Pt/TiO-MCF). Moreover, a Pt/TiO solid based on Evonik P25 was used as a reference. The biochars used as supports transferred, to a large extent, their physical and chemical properties to the final photocatalysts. The synthesized catalysts were tested for hydrogen production from aqueous glycerol photoreforming. The results indicated that a mesoporous nature and small particle size of the photocatalyst lead to better H production. The analysis of the operational reaction conditions revealed that the H evolution rate was not proportional to the mass of the photocatalyst used, since, at high photocatalyst loading, the hydrogen production decreased because of the light scattering and reflection phenomena that caused a reduction in the light penetration depth. When expressed per gram of TiO, the activity of Pt/TiO-PyCF is almost 4-times higher than that of Pt/TiO (1079 and 273 mmol H/g, respectively), which points to the positive effect of an adequate dispersion of a TiO phase on a carbonaceous support, forming a highly dispersed and homogeneously distributed titanium dioxide phase. Throughout a 12 h reaction period, the H production rate progressively decreases, while the CO production rate increases continuously. This behavior is compatible with an initial period when glycerol dehydrogenation to glyceraldehyde and/or dihydroxyacetone and hydrogen predominates, followed by a period in which comparatively slower C-C cleavage reactions begin to occur, thus generating both H and CO.
PubMed: 37177056
DOI: 10.3390/nano13091511 -
Biochemistry Jun 2023Four catalytic amino acids at triosephosphate isomerase (TIM) are highly conserved: N11, K13, H95, and E167. Asparagine 11 is the last of these to be characterized in...
Four catalytic amino acids at triosephosphate isomerase (TIM) are highly conserved: N11, K13, H95, and E167. Asparagine 11 is the last of these to be characterized in mutagenesis studies. The ND2 side chain atom of N11 is hydrogen bonded to the O-1 hydroxyl of enzyme-bound dihydroxyacetone phosphate (DHAP), and it sits in an extended chain of hydrogen-bonded side chains that includes T75' from the second subunit. The N11A variants of wild-type TIM from (TIM) and (TIM) undergo dissociation from the dimer to monomer under our assay conditions. Values of = 8 × 10 and 1 × 10 M, respectively, were determined for the conversion of monomeric N11A TIM and TIM into their homodimers. The N11A substitution at the variant of TIM previously stabilized by the E65Q substitution gives the N11A/E65Q variant that is stable to dissociation under our assay conditions. The X-ray crystal structure of N11A/E65Q TIM shows an active site that is essentially superimposable on that for wild-type TIM, which also has a glutamine at position 65. A comparison of the kinetic parameters for E65Q TIM and N11A/E65Q TIM-catalyzed reactions of ()-glyceraldehyde 3-phosphate (GAP) and (DHAP) shows that the N11A substitution results in a (13-14)-fold decrease in / for substrate isomerization and a similar decrease in for DHAP but only a 2-fold decrease in for GAP.
Topics: Triose-Phosphate Isomerase; Catalysis; Amino Acids; Hydrogen
PubMed: 37162263
DOI: 10.1021/acs.biochem.3c00133 -
Proceedings of the National Academy of... May 2023Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) contains an active site Cys and is one of the most sensitive cellular enzymes to oxidative inactivation and redox...
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) contains an active site Cys and is one of the most sensitive cellular enzymes to oxidative inactivation and redox regulation. Here, we show that inactivation by hydrogen peroxide is strongly enhanced in the presence of carbon dioxide/bicarbonate. Inactivation of isolated mammalian GAPDH by HO increased with increasing bicarbonate concentration and was sevenfold faster in 25 mM (physiological) bicarbonate compared with bicarbonate-free buffer of the same pH. HO reacts reversibly with CO to form a more reactive oxidant, peroxymonocarbonate (HCO), which is most likely responsible for the enhanced inactivation. However, to account for the extent of enhancement, we propose that GAPDH must facilitate formation and/or targeting of HCO to promote its own inactivation. Inactivation of intracellular GAPDH was also strongly enhanced by bicarbonate: treatment of Jurkat cells with 20 µM HO in 25 mM bicarbonate buffer for 5 min caused almost complete GAPDH inactivation, but no loss of activity when bicarbonate was not present. HO-dependent GAPDH inhibition in bicarbonate buffer was observed even in the presence of reduced peroxiredoxin 2 and there was a significant increase in cellular glyceraldehyde-3-phosphate/dihydroxyacetone phosphate. Our results identify an unrecognized role for bicarbonate in enabling HO to influence inactivation of GAPDH and potentially reroute glucose metabolism from glycolysis to the pentose phosphate pathway and NAPDH production. They also demonstrate what could be wider interplay between CO and HO in redox biology and the potential for variations in CO metabolism to influence oxidative responses and redox signaling.
Topics: Humans; Animals; Hydrogen Peroxide; Carbon Dioxide; Bicarbonates; Glyceraldehyde-3-Phosphate Dehydrogenases; Peroxiredoxins; Oxidation-Reduction; Mammals
PubMed: 37098065
DOI: 10.1073/pnas.2221047120 -
Molecules (Basel, Switzerland) Mar 20231,3-dihydroxyacetone (DHA) is an underrated bio-based synthon, with a broad range of reactivities. It is produced for the revalorization of glycerol, a major... (Review)
Review
1,3-dihydroxyacetone (DHA) is an underrated bio-based synthon, with a broad range of reactivities. It is produced for the revalorization of glycerol, a major side-product of the growing biodiesel industry. The overwhelming majority of DHA produced worldwide is intended for application as a self-tanning agent in cosmetic formulations. This review provides an overview of the discovery, physical and chemical properties of DHA, and of its industrial production routes from glycerol. Microbial fermentation is the only industrial-scaled route but advances in electrooxidation and aerobic oxidation are also reported. This review focuses on the plurality of reactivities of DHA to help chemists interested in bio-based building blocks see the potential of DHA for this application. The handling of DHA is delicate as it can undergo dimerization as well as isomerization reactions in aqueous solutions at room temperature. DHA can also be involved in further side-reactions, yielding original side-products, as well as compounds of interest. If this peculiar reactivity was harnessed, DHA could help address current sustainability challenges encountered in the synthesis of speciality polymers, ranging from biocompatible polymers to innovative polymers with cutting-edge properties and improved biodegradability.
Topics: Dihydroxyacetone; Glycerol; Fermentation; Oxidation-Reduction; Cosmetics
PubMed: 36985712
DOI: 10.3390/molecules28062724 -
Structure (London, England : 1993) Mar 2023Sulfoquinovose (SQ) is a key component of plant sulfolipids (sulfoquinovosyl diacylglycerols) and a major environmental reservoir of biological sulfur. Breakdown of SQ...
Sulfoquinovose (SQ) is a key component of plant sulfolipids (sulfoquinovosyl diacylglycerols) and a major environmental reservoir of biological sulfur. Breakdown of SQ is achieved by bacteria through the pathways of sulfoglycolysis. The sulfoglycolytic sulfofructose transaldolase (sulfo-SFT) pathway is used by gut-resident firmicutes and soil saprophytes. After isomerization of SQ to sulfofructose (SF), the namesake enzyme catalyzes the transaldol reaction of SF transferring dihydroxyacetone to 3C/4C acceptors to give sulfolactaldehyde and fructose-6-phosphate or sedoheptulose-7-phosphate. We report the 3D cryo-EM structure of SF transaldolase from Bacillus megaterium in apo and ligand bound forms, revealing a decameric structure formed from two pentameric rings of the protomer. We demonstrate a covalent "Schiff base" intermediate formed by reaction of SF with Lys89 within a conserved Asp-Lys-Glu catalytic triad and defined by an Arg-Trp-Arg sulfonate recognition triad. The structural characterization of the signature enzyme of the sulfo-SFT pathway provides key insights into molecular recognition of the sulfonate group of sulfosugars.
Topics: Transaldolase; Fructose-Bisphosphate Aldolase; Methylglucosides
PubMed: 36805128
DOI: 10.1016/j.str.2023.01.010 -
RSC Advances Jan 2023To realize sustainable societies, the production of organic compounds not based on fossil resources should be developed. Thus, C1 chemistry, utilizing one-carbon...
To realize sustainable societies, the production of organic compounds not based on fossil resources should be developed. Thus, C1 chemistry, utilizing one-carbon compounds as starting materials, has been of increasing importance. In particular, the formose reaction is promising because the reaction produces sugars (monosaccharides) from formaldehyde under basic conditions. On the other hand, since microwave (MW) induces the rotational motion of molecules, MW irradiation often improves the selectivity and efficiency of reactions. In this study, the formose reaction under MW irradiation was thus investigated under various conditions. The formose reaction proceeded very fast using 1.0 mol per kg formaldehyde and 55 mmol per kg calcium hydroxide (Ca(OH)) as a catalyst at a high set temperature (150 °C) for a short time (1 min) to form preferentially specific hexose and heptose. The major products were isolated by thin layer chromatography and characterized by mass spectroscopy and NMR. These characterization data elucidated that the hexose and heptose were 2-hydroxymethyl-1,2,4,5-tetrahydroxy-3-pentanone (C6*) and 2,4-bis(hydroxymethyl)-1,2,4,5-tetrahydroxy-3-pentanone (C7*), respectively. On the basis of these observations, as well as density functional theory calculations, a plausible reaction pathway was also discussed; once 1,3-dihydroxyacetone is formed, consecutive aldol reactions favorably occur to form C6* and C7*.
PubMed: 36756559
DOI: 10.1039/d2ra07249a -
Molecular Medicine (Cambridge, Mass.) Jan 2023Triosephosphate isomerase (TPI) is best known as a glycolytic enzyme that interconverts the 3-carbon sugars dihydroxyacetone phosphate (DHAP) and... (Review)
Review
Triosephosphate isomerase (TPI) is best known as a glycolytic enzyme that interconverts the 3-carbon sugars dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). TPI is an essential enzyme that is required for the catabolism of DHAP and a net yield of ATP from anaerobic glucose metabolism. Loss of TPI function results in the recessive disease TPI Deficiency (TPI Df). Recently, numerous lines of evidence suggest the TPI protein has other functions beyond glycolysis, a phenomenon known as moonlighting or gene sharing. Here we review the numerous functions ascribed to TPI, including recent findings of a nuclear role of TPI implicated in cancer pathogenesis and chemotherapy resistance.
Topics: Humans; Triose-Phosphate Isomerase; Anemia, Hemolytic, Congenital Nonspherocytic; Cell Nucleus; Carbohydrate Metabolism, Inborn Errors; Glucose
PubMed: 36721084
DOI: 10.1186/s10020-023-00612-x -
ACS Central Science Jan 2023Metal-organic frameworks (MOFs) with Brønsted acidity are an alternative solid acid catalyst for many important chemical and fuel processes. However, the nature of the...
Metal-organic frameworks (MOFs) with Brønsted acidity are an alternative solid acid catalyst for many important chemical and fuel processes. However, the nature of the Brønsted acidity on the MOF's metal cluster or center is underexplored. To design and optimize the acid strength and density in these MOFs, it is important to understand the origin of their acidity at the molecular level. In the present work, isoreticular MOFs, ZrNDI and HfNDI (NDI = ,'-bis(5-isophthalate)naphthalenediimide), were prepared as a prototypical system to unravel and compare their Brønsted and Lewis acid sites through an array of spectroscopic, computational, and catalytic characterization techniques. With the aid of solid-state nuclear magnetic resonance and density functional calculations, Hf oxo-clusters on HfNDI are quantitatively proved to possess a higher density Brønsted acid site, while ZrNDI-based MOFs display stronger and higher-population Lewis acidity. HfNDI-based MOFs exhibit a superior catalytic performance in activating dihydroxyacetone (DHA) and converting DHA to ethyl lactate, with 71.1% selectivity at 54.7% conversion after 6 h. The turnover frequency of BAS-dominated Hf-MOF in DHA conversion is over 50 times higher than that of ZSM-5, a strong BAS-based zeolite. It is worth noting that HfNDI is reported for the first time in the literature, which is an alternative platform catalyst for biorefining and green chemistry. The present study furthermore highlights the uniqueness of Hf-based MOFs in this important biomass-to-chemical transformation.
PubMed: 36712491
DOI: 10.1021/acscentsci.2c01140 -
Frontiers in Bioengineering and... 2022Engineering for efficient methanol assimilation is important for developing methanol as an emerging next-generation feedstock for industrial biotechnology. While recent...
Engineering for efficient methanol assimilation is important for developing methanol as an emerging next-generation feedstock for industrial biotechnology. While recent attempts to engineer as a synthetic methylotroph have achieved great success, most of these works are based on the engineering of the prokaryotic ribulose monophosphate (RuMP) pathway. In this study, we introduced a hybrid methanol assimilation pathway which consists of prokaryotic methanol dehydrogenase (Mdh) and eukaryotic xylulose monophosphate (XuMP) pathway enzyme dihydroxyacetone synthase (Das) into and reprogrammed metabolism to improve methanol assimilation by combining rational design and adaptive laboratory evolution. By deletion and down-regulation of key genes in the TCA cycle and glycolysis to increase the flux toward the cyclic XuMP pathway, methanol consumption and the assimilation of methanol to biomass were significantly improved. Further improvements in methanol utilization and cell growth were achieved adaptive laboratory evolution and a final evolved strain can grow on methanol with only 0.1 g/L yeast extract as co-substrate. C-methanol labeling assay demonstrated significantly higher labeling in intracellular metabolites in glycolysis, TCA cycle, pentose phosphate pathway, and amino acids. Transcriptomics analysis showed that the expression of , and part of pentose phosphate pathway genes were highly up-regulated, suggesting that the rational engineering strategies and adaptive evolution are effective for activating the cyclic XuMP pathway. This study demonstrated the feasibility and provided new strategies to construct synthetic methylotrophy of based on the hybrid methanol assimilation pathway with Mdh and Das.
PubMed: 36704306
DOI: 10.3389/fbioe.2022.1089639