4,706 results on '"succinates"'
Search Results
2. THE EFFECTS OF SERA FROM SCHIZOPHRENIC SUBJECTS ON THE OXIDATION OF SUCCINATE AND ALPHA-KETOGLUTARATE.
- Author
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LEES H, GREENWOOD DJ, FROHMAN CE, BECKETT PG, and GOTTLIEB JS
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- Animals, Rats, Biochemical Phenomena, Biochemistry, Biomedical Research, Blood, Electron Transport Complex II, Erythrocytes, Histological Techniques, Ketoglutaric Acids, Lactates, Liver, Metabolism, Oxidation-Reduction, Poultry, Pyruvates, Schizophrenia, Succinate Dehydrogenase, Succinates, Succinic Acid
- Published
- 1964
3. STUDIES ON THE METABOLISM OF ECHINOCOCCUS GRANULOSUS. VII. REACTIONS OF THE TRICARBOXYLIC ACID CYCLE IN E. GRANULOSUS SCOLICES.
- Author
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AGOSIN M and REPETTO Y
- Subjects
- Animals, Acetates, Amino Acids, Biochemical Phenomena, Biochemistry, Carbon Dioxide, Carbon Isotopes, Citric Acid Cycle, Echinococcus, Echinococcus granulosus, Metabolism, Oxidoreductases, Research, Succinates
- Published
- 1963
- Full Text
- View/download PDF
4. [ON THE SIGNIFICANCE OF CERTAIN AMINO ACID RESIDUES IN THE PEPSIN MOLECULE FOR ITS ENZYMATIC ACTIVITY].
- Author
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LOKSHINA LA and OREKHOVICH VN
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- Amino Acids, Biochemical Phenomena, Biochemistry, Iodoacetates, Methionine, Pepsin A, Pharmacology, Research, Succinates, Tryptophan, Tyrosine, Urea
- Published
- 1964
5. REGULATION OF BACTERIAL ENZYME SYNTHESIS BY INDUCTION AND REPRESSION.
- Author
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CLARKE PH and BRAMMAR WJ
- Subjects
- Biochemical Phenomena, Amides, Amidohydrolases, Biochemistry, Pseudomonas aeruginosa, Research, Succinates
- Published
- 1964
- Full Text
- View/download PDF
6. STUDIES ON ESSENTIAL FATTY ACID DEFICIENCY. EFFECT OF THE DEFICIENCY ON THE LIPIDS IN LIVER MITOCHONDRIA AND OXIDATIVE PHOSPHORYLATION.
- Author
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BIRAN LA, BARTLEY W, CARTER CW, and RENSHAW A
- Subjects
- Rats, Biochemical Phenomena, Biochemistry, Biological Products, Chromatography, Deficiency Diseases, Fatty Acids, Fatty Acids, Essential, Flax, Lipids, Liver cytology, Metabolism, Mitochondria, Mitochondria, Liver, Oxidative Phosphorylation, Phospholipids, Pyruvates, Research, Succinates
- Abstract
1. Dietary deficiency of essential fatty acids results in a twofold increase in the neutral lipid content of liver mitochondria as compared with the corresponding value for stock-fed rats. 2. Deficiency produces changes in the pattern of the constituent fatty acids of the main phospholipid fractions of liver mitochondria which are similar to those previously reported for the lipids of whole liver. There is a fall in the content of C(18:2) acid and to a smaller extent of C(20:4) acid associated with a rise of C(16:1), C(18:1) and C(20:3) acids. 3. Deficiency results in small decreases in the phosphorylation quotients of liver mitochondria during oxidation of succinate and pyruvate, but the values lie within the range reported for normal mitochondria. Mitochondrial respiration with succinate is decreased as a result of deficiency but no change was observed with pyruvate as substrate.
- Published
- 1965
- Full Text
- View/download PDF
7. [DIFFERENT BIOCHEMICAL BEHAVIOR OF 2 STRAINS OF STAPHYLOCOCCUS AUREUS WITH DIVERSE RADIATION RESISTANCE AFTER IRRADIATION WITH TRITIATED WATER].
- Author
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GIOVANNOZZI-SERMANNI G and CACCIARI I
- Subjects
- Biochemical Phenomena, Biochemistry, Catalase, Coenzyme A, Electron Transport Complex II, Phosphotransferases, Radiation Effects, Research, Staphylococcal Infections, Staphylococcus, Staphylococcus aureus, Succinate Dehydrogenase, Succinates, Tritium, Water
- Published
- 1964
8. THE DEAGGREGATION OF BOVINE LENS ALPHA-CRYSTALLIN.
- Author
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SPECTOR A and KATZ E
- Subjects
- Animals, Cattle, Biochemical Phenomena, Biochemistry, Crystallins, Eye Proteins, Guanidine, Guanidines, Hydrogen-Ion Concentration, Lens, Crystalline, Molecular Weight, Research, Succinates, Ultracentrifugation, Urea, alpha-Crystallins
- Published
- 1965
9. A MUTANT ENZYME IN NEUROSPORA CRASSA INTERCONVERTIBLE BETWEEN ELECTROPHORETICALLY DISTINCT ACTIVE AND INACTIVE FORMS.
- Author
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SUNDARAM TK and FINCH AM Jr
- Subjects
- Biochemical Phenomena, Biochemistry, Edetic Acid, Electrophoresis, Glutamate Dehydrogenase, Mutation, NADP, Neurospora, Neurospora crassa, Research, Succinates
- Published
- 1964
- Full Text
- View/download PDF
10. Hypoxic Preconditioning Averts Sporadic Alzheimer's Disease-Like Phenotype in Rats: A Focus on Mitochondria
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Sónia C. Correia, Marco G. Alves, Pedro F. Oliveira, Gemma Casadesus, Joseph LaManna, George Perry, and Paula I. Moreira
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Physiology ,Clinical Biochemistry ,Succinates ,Cell Biology ,DNA, Mitochondrial ,Biochemistry ,Streptozocin ,Mitochondria ,Rats ,Disease Models, Animal ,Phenotype ,Glutamates ,Alzheimer Disease ,Glial Fibrillary Acidic Protein ,Lactates ,Animals ,General Earth and Planetary Sciences ,Hypoxia ,Molecular Biology ,Inositol ,General Environmental Science - Abstract
biAims:/i/bBrief episodes of sublethal hypoxia reprogram brain response to face possible subsequent lethal stimuli by triggering adaptive and prosurvival events-a phenomenon denominated hypoxic preconditioning (HP). To date, the potential therapeutic implications of HP to forestall sporadic Alzheimer's disease (sAD) pathology remain unexplored. Using a well-established protocol of HP and focusing on hippocampus as a first brain region affected in AD, this study was undertaken to investigate the potential protective effects of HP in a sAD rat model induced by the intracerebroventricular (icv) administration of streptozotocin (STZ) and to uncover the mitochondrial adaptations underlying this nonpharmacological strategy.biResults:/i/bHP prevented the memory and learning deficits as well as tau pathology in the icvSTZ rat model. HP also attenuated icvSTZ-related reactive astrogliosis, as noted by increased glial fibrillary acidic protein immunoreactivity and myo-inositol levels. Notably, HP abrogated the icvSTZ-related impaired energy metabolism and oxidative damage. Particularly, HP averted increased lactate, glutamate, and succinate levels, and decreased mitochondrial respiratory chain function and mitochondrial DNA content. Concerning mitochondrial adaptations underlying HP-triggered tolerance to icvSTZ, preconditioned hippocampal mitochondria displayed an enhanced complex II-energized mitochondrial respiration, which resulted from a coordinated interaction between mitochondrial biogenesis and fusion-fission. Mitochondrial biogenesis was stimulated immediately after HP, whereas in a latter phase mitochondrial fusion-fission events are modulated favoring the generation of elongated mitochondria.biInnovation and Conclusion:/i/bOverall, these results demonstrate for the first time that HP prevents the sAD-like phenotype, in part, by targeting mitochondria emerging as a preventive strategy in the context of AD.iAntioxid. Redox Signal/i. 37, 739-757.
- Published
- 2022
11. The structure of succinyl-CoA synthetase bound to the succinyl-phosphate intermediate clarifies the catalytic mechanism of ATP-citrate lyase
- Author
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Ji Huang and Marie E. Fraser
- Subjects
Succinic Acid ,Biophysics ,Oxo-Acid-Lyases ,Nucleosides ,Succinates ,Crystallography, X-Ray ,Condensed Matter Physics ,Biochemistry ,Diphosphates ,Adenosine Triphosphate ,Acetyl Coenzyme A ,Multienzyme Complexes ,Structural Biology ,Succinate-CoA Ligases ,ATP Citrate (pro-S)-Lyase ,Genetics ,Humans ,Magnesium ,Acyl Coenzyme A ,Guanosine Triphosphate - Abstract
Succinyl-CoA synthetase (SCS) catalyzes a three-step reaction in the citric acid cycle with succinyl-phosphate proposed as a catalytic intermediate. However, there are no structural data to show the binding of succinyl-phosphate to SCS. Recently, the catalytic mechanism underlying acetyl-CoA production by ATP-citrate lyase (ACLY) has been debated. The enzyme belongs to the family of acyl-CoA synthetases (nucleoside diphosphate-forming) for which SCS is the prototype. It was postulated that the amino-terminal portion catalyzes the full reaction and the carboxy-terminal portion plays only an allosteric role. This interpretation was based on the partial loss of the catalytic activity of ACLY when Glu599 was mutated to Gln or Ala, and on the interpretation that the phospho-citryl-CoA intermediate was trapped in the 2.85 Å resolution structure from cryogenic electron microscopy (cryo-EM). To better resolve the structure of the intermediate bound to the E599Q mutant, the equivalent mutation, E105αQ, was made in human GTP-specific SCS. The structure of the E105αQ mutant shows succinyl-phosphate bound to the enzyme at 1.58 Å resolution when the mutant, after phosphorylation in solution by Mg2+-ATP, was crystallized in the presence of magnesium ions, succinate and desulfo-CoA. The E105αQ mutant is still active but has a specific activity that is 120-fold less than that of the wild-type enzyme, with apparent Michaelis constants for succinate and CoA that are 50-fold and 11-fold higher, respectively. Based on this high-resolution structure, the cryo-EM maps of the E599Q ACLY complex reported previously should have revealed the binding of citryl-phosphate and CoA and not phospho-citryl-CoA.
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- 2022
12. Plasma metabolomic profiling reflects the malnourished and chronic inflammatory state in recessive dystrophic epidermolysis bullosa
- Author
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Ya-Fen, Chen, Hsin-Chin, Lu, Ping-Chen, Hou, Yu-Ching, Lin, Wilson Jr, Aala, Alexandros, Onoufriadis, John A, McGrath, Ying-Lan, Chen, and Chao-Kai, Hsu
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Inflammation ,Glutamine ,Phenylalanine ,Malnutrition ,Tryptophan ,Succinates ,Dermatology ,Fibrosis ,Biochemistry ,Epidermolysis Bullosa Dystrophica ,Glutamates ,Tandem Mass Spectrometry ,Humans ,Tyrosine ,Molecular Biology ,Kynurenine ,Chromatography, Liquid - Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder characterized by skin fragility, chronic inflammation, malnutrition, and fibrosis. Metabolomics is an emerging investigative field that helps elucidate disease pathophysiology and identify biomarkers. However, previous metabolomic studies in RDEB are limited.To investigate the plasma metabolomic profiles in RDEB patients.We recruited 10 RDEB patients and 10 age-/gender-matched healthy controls. Peripheral blood samples were collected and plasma metabolomic profiling was performed by LC-MS/MS analysis. MS data processing and compound identification were executed by MS-DIAL. Enrichment analysis was performed by MetaboAnalyst 5.0.Metabolomic analyses demonstrated that most amino acid levels were downregulated in RDEB patients, and the extent of insufficiency correlated with clinical severity. Several metabolites were dysregulated in RDEB, including glutamine and glutamate metabolism, tryptophan-to-kynurenine ratio, phenylalanine-to-tyrosine ratio, and succinate accumulation.The study was limited by small case numbers and the unrepresentativeness of a single time-point blood sample.Our study demonstrated the altered metabolomic profiles in RDEB, reflecting the disease severity, the chronic inflammatory and malnourished status, while the fibrotic signatures were not evident.
- Published
- 2022
13. 4-Octyl itaconate suppresses the osteogenic response in aortic valvular interstitial cells via the Nrf2 pathway and alleviates aortic stenosis in mice with direct wire injury
- Author
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Xin, Peng, Shuwen, Su, Jingxin, Zeng, Kaiji, Xie, Xi, Yang, Gaopeng, Xian, Zezhou, Xiao, Peng, Zhu, Shaoyi, Zheng, Dingli, Xu, and Qingchun, Zeng
- Subjects
NF-E2-Related Factor 2 ,Calcinosis ,Succinates ,Aortic Valve Stenosis ,Endoplasmic Reticulum Stress ,Biochemistry ,Mice ,Osteogenesis ,Aortic Valve ,Physiology (medical) ,Animals ,Reactive Oxygen Species ,Biomarkers ,Cells, Cultured - Abstract
Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease in older individuals, but there is a lack of drug treatment. The cellular biological mechanisms of CAVD are still unclear. Oxidative stress and endoplasmic reticulum stress (ER stress) have been suggested to be involved in the progression of CAVD. Many studies have demonstrated that 4-octyl itaconate (OI) plays beneficial roles in limiting inflammation and oxidative injury. However, the potential role of OI in CAVD has not been thoroughly explored. Thus, we investigated OI-mediated modulation of ROS generation and endoplasmic reticulum stress to inhibit osteogenic differentiation in aortic valve interstitial cells (VICs). In our study, calcified aortic valves showed increased levels of ER stress and superoxide anion, as well as abnormal expression of Hmox1 and NQO1. In VICs, OI activated the Nrf2 signaling cascade and contributed to Nrf2 stabilization and nuclear translocation, thus augmenting the expression of genes downstream of Nrf2 (Hmox1 and NQO1). Moreover, OI ameliorated osteogenic medium (OM)-induced ROS production, mitochondrial ROS levels and the loss of mitochondrial membrane potential in VICs. Furthermore, OI attenuated the OM-induced upregulation of ER stress markers, osteogenic markers and calcium deposition, which were blocked by the Nrf2-specific inhibitor ML385. Interestingly, we found that OM-induced ER stress and osteogenic differentiation were ROS-dependent and that Hmox1 silencing triggered ROS production, ER stress and elevated osteogenic activity, which were inhibited by NAC. Overexpression of NQO1 mediated by adenovirus vectors significantly suppressed OM-induced ER stress and osteogenic markers. Collectively, these results showed the anti-osteogenic effects of OI on AVICs by regulating the generation of ROS and ER stress by activating the Nrf2 signaling pathway. Furthermore, OI alleviated aortic stenosis in a mouse model with direct wire injury. Due to its antioxidant properties, OI could be a potential drug for the prevention and/or treatment of CAVD.
- Published
- 2022
14. Insights into the development of pentylenetetrazole-induced epileptic seizures from dynamic metabolomic changes
- Author
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Xue Zhao, Peixuan Cheng, Ru Xu, Kaili Meng, Sha Liao, Pu Jia, Xiaohui Zheng, and Chaoni Xiao
- Subjects
Alanine ,Epilepsy ,Succinates ,Valine ,Ketone Bodies ,Creatine ,Biochemistry ,Rats ,Disease Models, Animal ,Cellular and Molecular Neuroscience ,Glucose ,Glutamates ,Leucine ,Seizures ,Creatinine ,Lactates ,Animals ,Pentylenetetrazole ,Anticonvulsants ,Citrates ,Neurology (clinical) ,Asparagine ,Isoleucine ,Pyruvates - Abstract
Epilepsy is often considered to be a progressive neurological disease, and the nature of this progression remains unclear. Understanding the overall and common metabolic changes of epileptic seizures can provide novel clues for their control and prevention. Herein, a chronic kindling animal model was established to obtain generalized tonic-clonic seizures via the repeated injections of pentylenetetrazole (PTZ) at subconvulsive dose. Dynamic metabolomic changes in plasma and urine from PTZ-kindled rats at the different kindling phases were explored using NMR-based metabolomics, in combination with behavioral assessment, brain neurotransmitter measurement, electroencephalography and histopathology. The increased levels of glucose, lactate, glutamate, creatine and creatinine, together with the decreased levels of pyruvate, citrate and succinate, ketone bodies, asparagine, alanine, leucine, valine and isoleucine in plasma and/or urine were involved in the development and progression of seizures. These altered metabolites reflected the pathophysiological processes including the compromised energy metabolism, the disturbed amino acid metabolism, the peripheral inflammation and changes in gut microbiota functions. NMR-based metabolomics could provide brain disease information by the dynamic plasma and urinary metabolic changes during chronic epileptic seizures, yielding classification of seizure stages and profound insights into controlling epilepsy via targeting deficient energy metabolism.
- Published
- 2022
15. Nutritional and metabolic signalling through<scp>GPCRs</scp>
- Author
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Elisa Pardella, Luigi Ippolito, Elisa Giannoni, and Paola Chiarugi
- Subjects
Structural Biology ,Lactates ,Genetics ,Biophysics ,Succinates ,Cell Biology ,Amino Acids ,Molecular Biology ,Biochemistry ,Hormones ,Receptors, G-Protein-Coupled - Abstract
Deregulated metabolism is a well-known feature of several challenging diseases, including diabetes, obesity and cancer. Besides their important role as intracellular bioenergetic molecules, dietary nutrients and metabolic intermediates are released in the extracellular environment. As such, they may achieve unconventional roles as hormone-like molecules by activating cell surface G-protein-coupled receptors (GPCRs) that regulate several pathophysiological processes. In this review, we provide an insight into the role of lactate, succinate, fatty acids, amino acids as well as ketogenesis-derived and β-oxidation-derived intermediates as extracellular signalling molecules. Moreover, the mechanisms by which their cognate metabolite-sensing GPCRs integrate nutritional and metabolic signals with specific intracellular pathways will be described. A better comprehension of these aspects is of fundamental importance to identify GPCRs as novel druggable targets.
- Published
- 2022
16. Comparative study of free respiration in liver mitochondria during oxidation of various electron donors and under conditions of shutdown of complex III of the respiratory chain
- Author
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Victor N. Samartsev, Alena A. Semenova, Andrey N. Ivanov, and Mikhail V. Dubinin
- Subjects
Respiration ,Succinic Acid ,Biophysics ,Glutamic Acid ,Electrons ,Mitochondria, Liver ,Succinates ,Cell Biology ,Biochemistry ,Electron Transport ,Electron Transport Complex III ,Oxygen Consumption ,Protons ,Molecular Biology - Abstract
The present work shows that the rate of free respiration of liver mitochondria (in the absence of ATP synthesis (state 4) during the oxidation of succinate is 1.7 times higher than during the oxidation of glutamate with malate. In turn, in the case of oxidation of ferrocyanide with ascorbate, this value is 3.1 times greater than in the case of succinate oxidation. A similar pattern is also observed upon stimulation of free respiration by low concentrations (5 and 10 μM) of the protonophore uncoupler 2,4-dinitrophenol (DNP). It is found that the passive leakage rate of protons in state 4 is the same if the H
- Published
- 2022
17. Ag/LDH-itaconic acid-gellan gam nanocomposites: Facile and green synthesis, characterization, and excellent catalytic reduction of 4-nitrophenol
- Author
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Mohammad Dinari and Shirin Shabani
- Subjects
Silver ,Nanocomposite ,Polysaccharides, Bacterial ,Metal Nanoparticles ,Succinates ,Selective catalytic reduction ,General Medicine ,Aminophenols ,Biochemistry ,Catalysis ,Gellan gum ,Silver nanoparticle ,Nanocomposites ,Nitrophenols ,Kinetics ,chemistry.chemical_compound ,Reaction rate constant ,chemistry ,Chemical engineering ,Structural Biology ,Hydroxides ,Hydroxide ,Itaconic acid ,Molecular Biology - Abstract
The catalytic reduction reaction is one of the most commonly used solutions to convert high-risk contaminants into safe or low-risk materials. Today, with the increasing water pollution, the urgent need for efficient and effective catalysts is felt more than ever. For this purpose, for the first time, a green catalyst composed of silver nanoparticles anchored on itaconic acid-modified Ca-Al layered double hydroxide/gellan gum nanocomposite (Ag/LDH-ITA-GG NC) was prepared from a green approach without the use of any toxic organic solvents. To gain an in-depth insight into the physicochemical properties of the catalyst, different techniques including nitrogen adsorption-desorption isotherms, FESEM/mapping, FTIR, TGA, and XRD were used. The catalytic performance of the Ag/LDH-ITA-GG NC toward 4-nitrophenol reduction by NaBH4 was investigated. The calculated values of the apparent rate constant for this reaction are 0.2142 min−1 (for 1.0 mg of the catalyst), 0.2375 min−1 (for 3.0 mg of the catalyst), and 0.2550 min−1 (for 5.0 mg of the catalyst), indicating that the catalytic conversion of 4-nitrophenol to 4-aminophenol on the Ag/LDH-ITA-GG NC catalyst follows the pseudo-first-order kinetics and is comparable to the previous findings in the literature. The results of this study indicated that Ag/LDH-ITA-GG NC can potentially be utilized as an auspicious high efficient green catalyst for the reduction of pollutants like 4-nitrophenol.
- Published
- 2021
18. Evaluation of gum ghatti-g-poly(itaconic acid) magnetite nanocomposite as an adsorbent material for water purification
- Author
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Vishalakshi Badalamoole and Prajwal Kulal
- Subjects
Polymers ,Wastewater ,Biochemistry ,Nanocomposites ,Water Purification ,chemistry.chemical_compound ,Adsorption ,Structural Biology ,Desorption ,Plant Gums ,Zeta potential ,Freundlich equation ,Itaconic acid ,Coloring Agents ,Magnetite Nanoparticles ,Molecular Biology ,Magnetite ,Nanocomposite ,Rhodamines ,Succinates ,General Medicine ,Ferrosoferric Oxide ,Kinetics ,chemistry ,Chemical engineering ,Mesoporous material ,Water Pollutants, Chemical - Abstract
A porous hydrogel nanocomposite has been made by grafting poly(itaconic acid) on the polysaccharide, gum ghatti and by embedding magnetite nanoparticles in the copolymer gel matrix. This novel functional material Ggh-g-PIA/Fe3O4 was characterized by FTIR, TGA, SEM, EDS, XRD, BET, Zeta potential measurements and VSM techniques. The nanocomposite possesses mesoporous structure with high surface area and exhibits super-paramagnetic behavior due to the presence of magnetite nanoparticles. The hydrogel nanocomposite was evaluated as an adsorbent material for removal of dyes and divalent metal ions. Significant adsorption capacities of 410.2, 387.6, 416.5 and 401.4 mg g−1 towards methylene blue, rhodamine 6G, Cu (II) and Hg (II) ions respectively were observed. The adsorption isotherms were well described by the Freundlich isotherm model and kinetic studies demonstrated the adsorption to be a pseudo second order kinetic process. Intraparticle diffusion model suggested adsorption to occur by a multi-step diffusion process. Thermodynamic studies indicated a spontaneous and endothermic adsorption. Further, the desorption study indicated the possibility of successful regeneration of the adsorbent. A high removal efficiency, recyclability, convenient recovery after use due to the magnetic nature makes this polysaccharide based nanocomposite an environment friendly adsorbent material for water purification.
- Published
- 2021
19. The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors
- Author
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Harry A. Dailey, Hector A. Bergonia, James E. Cox, John D. Phillips, Amy E. Medlock, and Jason R. Marcero
- Subjects
chemistry.chemical_classification ,Methionine ,Macrophages ,Glyoxylate cycle ,Succinates ,Heme ,Hematology ,ALAS2 ,Amino acid ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Glycolysis ,Threonine ,Isoleucine - Abstract
As part of the inflammatory response by macrophages, Irg1 is induced, resulting in millimolar quantities of itaconate being produced. This immunometabolite remodels the macrophage metabolome and acts as an antimicrobial agent when excreted. Itaconate is not synthesized within the erythron but instead may be acquired from central macrophages within the erythroid island. Previously, we reported that itaconate inhibits hemoglobinization of developing erythroid cells. Herein we show that this action is accomplished by inhibition of tetrapyrrole synthesis. In differentiating erythroid precursors, cellular heme and protoporphyrin IX synthesis are reduced by itaconate at an early step in the pathway. In addition, itaconate causes global alterations in cellular metabolite pools, resulting in elevated levels of succinate, 2-hydroxyglutarate, pyruvate, glyoxylate, and intermediates of glycolytic shunts. Itaconate taken up by the developing erythron can be converted to itaconyl–coenzyme A (CoA) by the enzyme succinyl-CoA:glutarate-CoA transferase. Propionyl-CoA, propionyl-carnitine, methylmalonic acid, heptadecanoic acid, and nonanoic acid, as well as the aliphatic amino acids threonine, valine, methionine, and isoleucine, are increased, likely due to the impact of endogenous itaconyl-CoA synthesis. We further show that itaconyl-CoA is a competitive inhibitor of the erythroid-specific 5-aminolevulinate synthase (ALAS2), the first and rate-limiting step in heme synthesis. These findings strongly support our hypothesis that the inhibition of heme synthesis observed in chronic inflammation is mediated not only by iron limitation but also by limitation of tetrapyrrole synthesis at the point of ALAS2 catalysis by itaconate. Thus, we propose that macrophage-derived itaconate promotes anemia during an inflammatory response in the erythroid compartment.
- Published
- 2021
20. Inactive pseudoenzyme subunits in heterotetrameric BbsCD, a novel short‐chain alcohol dehydrogenase involved in anaerobic toluene degradation
- Author
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Yann Geisselbrecht, Lars-Oliver Essen, Marie-Luise Lippert, Silke von Horsten, Iris Schall, Karola Schühle, and Johann Heider
- Subjects
Models, Molecular ,Thauera ,Thauera aromatica ,Stereochemistry ,Dehydrogenase ,Nicotinamide adenine dinucleotide ,Biochemistry ,Short Chain Dehydrogenase-Reductases ,chemistry.chemical_compound ,Sulfhydryl Compounds ,Molecular Biology ,Alcohol dehydrogenase ,chemistry.chemical_classification ,Molecular Structure ,biology ,Chemistry ,Active site ,Succinates ,Cell Biology ,biology.organism_classification ,Heterotetramer ,Enzyme ,Biocatalysis ,biology.protein ,Acyl Coenzyme A ,NAD+ kinase ,Toluene - Abstract
Anaerobic toluene degradation proceeds by fumarate addition to produce (R)-benzylsuccinate as first intermediate, which is further degraded via β-oxidation by five enzymes encoded in the conserved bbs operon. This study characterizes two enzymes of this pathway, (E)-benzylidenesuccinyl-CoA hydratase (BbsH), and (S,R)-2-(α-hydroxybenzyl)succinyl-CoA dehydrogenase (BbsCD) from Thauera aromatica. BbsH, a member of the enoyl-CoA hydratase family, converts (E)-benzylidenesuccinyl-CoA to 2-(α-hydroxybenzyl)succinyl-CoA and was subsequently used in a coupled enzyme assay with BbsCD, which belongs to the short-chain dehydrogenases/reductase (SDR) family. The BbsCD crystal structure shows a C2-symmetric heterotetramer consisting of BbsC2 and BbsD2 dimers. BbsD subunits are catalytically active and capable of binding NAD+ and substrate, whereas BbsC subunits represent built-in pseudoenzyme moieties lacking all motifs of the SDR family required for substrate binding or catalysis. Molecular modeling studies predict that the active site of BbsD is specific for conversion of the (S,R)-diastereomer of 2-(α-hydroxybenzyl)succinyl-CoA to (S)-2-benzoylsuccinyl-CoA by hydride transfer to the re-face of nicotinamide adenine dinucleotide (NAD)+ . Furthermore, BbsC subunits are not engaged in substrate binding and merely serve as scaffold for the BbsD dimer. BbsCD represents a novel clade of related enzymes within the SDR family, which adopt a heterotetrameric architecture and catalyze the β-oxidation of aromatic succinate adducts.
- Published
- 2021
21. Porous layer open‐tubular column with styrene and itaconic acid‐copolymerized polymer as stationary phase for capillary electrochromatography–mass spectrometry
- Author
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Yikun Liu, Wei Zhou, Wenqi Sun, Zilin Chen, and Xinhong Yu
- Subjects
Capillary electrochromatography ,Materials science ,Capillary action ,Clinical Biochemistry ,Succinates ,Biochemistry ,Analytical Chemistry ,Styrene ,chemistry.chemical_compound ,chemistry ,Polymerization ,Chemical engineering ,Capillary Electrochromatography ,Tandem Mass Spectrometry ,Specific surface area ,Alkylbenzenes ,Itaconic acid ,Theoretical plate - Abstract
Enhancing the specific surface area of stationary phase is important in chromatographic science, especially in open-tubular column in which the coating only exists on the inner surface. In this work, a porous layer open-tubular (PLOT) column with stationary phase of styrene and itaconic acid-copolymerized polymer was developed. Thermal-initiated polymerization method with strategies like controlling the ratio of reaction reagents to solvents and reaction time, confinement by the narrow inner diameter of capillary were used for preparing the stationary phase with uniform structure and relatively thick layer. Due to the high separation efficiency and capacity, the PLOT column was used for capillary electrochromatography (CEC) separation of multiple groups of analytes like alkylbenzenes, phenyl amines, phenols, vanillins, and sulfonamides with theoretical plates (N) up to 1,54,845 N/m. In addition, due to high permeability of the CEC column and large electroosmotic flow mobility generated by abundant carboxyl groups in the coating material, the PLOT-CEC column was successfully coupled with mass spectrometry (MS) through a sheath flow interface. The developed PLOT-CEC-MS method was used for the analysis of antiseptics like parabens and herbicides like pyridines.
- Published
- 2021
22. Protective Role of 4-Octyl Itaconate in Murine LPS/D-GalN-Induced Acute Liver Failure via Inhibiting Inflammation, Oxidative Stress, and Apoptosis
- Author
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Kaixiong Tao, Yaxin Wang, Yuping Yin, Peng Zhang, Ruidong Li, and Wenchang Yang
- Subjects
Lipopolysaccharides ,Male ,Aging ,Article Subject ,NF-E2-Related Factor 2 ,Anti-Inflammatory Agents ,Aspartate transaminase ,Apoptosis ,Galactosamine ,Pharmacology ,Protective Agents ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Proinflammatory cytokine ,Lipid peroxidation ,Superoxide dismutase ,Mice ,chemistry.chemical_compound ,medicine ,Animals ,Inflammation ,chemistry.chemical_classification ,Reactive oxygen species ,QH573-671 ,biology ,Chemistry ,NF-kappa B ,Succinates ,Cell Biology ,General Medicine ,Liver Failure, Acute ,Mice, Inbred C57BL ,Oxidative Stress ,Alanine transaminase ,biology.protein ,Tumor necrosis factor alpha ,Cytology ,Oxidative stress ,Signal Transduction ,Research Article - Abstract
Oxidative stress, inflammation, and apoptosis are crucial in the pathogenesis of acute liver failure (ALF). 4-Octyl itaconate (OI) showed antioxidative and anti-inflammatory properties in many disease models. However, its role in lipopolysaccharide- (LPS-)/D-galactosamine- (D-GalN-) induced ALF is still not investigated. Here, we established an ALF murine model induced by LPS/D-GalN administration. And we found that OI improved survival rate in the murine ALF model. Our results also showed that OI alleviated LPS/D-GalN-induced hepatic histopathological injury and reduced the serum activities of alanine transaminase and aspartate transaminase. Moreover, OI reduced serum levels of proinflammatory cytokines such as monocyte chemotactic protein-1, tumor necrosis factors-α, and interlukin-6. Additionally, OI mitigated oxidative stress and alleviated lipid peroxidation in a murine model of ALF. This was evaluated by a reduction of thiobarbituric acid reactive substances (TBARS) in liver tissues. In addition, OI increased the ratio of reduced glutathione/oxidized glutathione and the activities of antioxidant enzymes including catalase and superoxide dismutase. Moreover, the apoptosis of hepatocytes in the liver was inhibited by OI. Furthermore, we found that OI inhibited LPS-induced nuclear translocation and activation of factor-kappa B (NF-κB) p65 in macrophages which could be inhibited by OI-induced activation of nuclear factor erythroid-2-related factor (Nrf2) signaling. Additionally, D-GalN-induced reactive oxygen species (ROS) generation and apoptosis in hepatocytes were inhibited by OI-induced activation of Nrf2 signaling. Therefore, the underlying mechanism for OI’s protective effect in LPS/D-GalN-induced ALF may be associated with deactivation of NF-κB signaling in macrophages to reduce inflammation and inhibition of ROS-related hepatocyte apoptosis by activating Nrf2. In conclusion, OI showed a protective role in LPS/D-GalN-induced ALF by reducing inflammation, enhancing antioxidant capacity, and inhibiting cell apoptosis.
- Published
- 2021
23. Protein targeting by the itaconate family in immunity and inflammation
- Author
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Emily A. Day and Luke A.J. O'Neill
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Inflammation ,Mice ,Kelch-Like ECH-Associated Protein 1 ,NF-E2-Related Factor 2 ,Animals ,Succinates ,Cell Biology ,Molecular Biology ,Biochemistry - Abstract
Immune cells are metabolically plastic and respond to inflammatory stimuli with large shifts in metabolism. Itaconate is one of the most up-regulated metabolites in macrophages in response to the gram negative bacterial product LPS. As such, itaconate has recently been the subject of intense research interest. The artificial derivatives, including 4-Octyl Itaconate (4-OI) and Dimethyl Itaconate (DI) and naturally produced isomers, mesaconate and citraconate, have been tested in relation to itaconate biology with similarities and differences in the biochemistry and immunomodulatory properties of this family of compounds emerging. Both itaconate and 4-OI have been shown to modify cysteines on a range of target proteins, with the modification being linked to a functional change. Targets include KEAP1 (the NRF2 inhibitor), GAPDH, NLRP3, JAK1, and the lysosomal regulator, TFEB. 4-OI and DI are more electrophilic, and are therefore stronger NRF2 activators, and inhibit the production of Type I IFNs, while itaconate inhibits SDH and the dioxygenase, TET2. Additionally, both itaconate and derivates have been shown to be protective across a wide range of mouse models of inflammatory and infectious diseases, through both distinct and overlapping mechanisms. As such, continued research involving the comparison of itaconate and related molecules holds exciting prospects for the study of cysteine modification and pathways for immunomodulation and the potential for new anti-inflammatory therapeutics.
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- 2022
24. Desulfofustis limnaeus sp. nov., a freshwater sulfate-reducing bacterium isolated from marsh soil
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Miho Watanabe, Ayaka Takahashi, Hisaya Kojima, Naoyuki Miyata, and Manabu Fukui
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DNA, Bacterial ,Deltaproteobacteria ,Formates ,Sulfates ,Fatty Acids ,Malates ,Thiosulfates ,Fresh Water ,Succinates ,Sequence Analysis, DNA ,General Medicine ,Biochemistry ,Microbiology ,Bacterial Typing Techniques ,Soil ,Fumarates ,RNA, Ribosomal, 16S ,Wetlands ,Lactates ,Genetics ,Sulfites ,Molecular Biology ,Phylogeny ,Sulfur ,Hydrogen - Abstract
A novel sulfate-reducing bacterium, strain PPLL
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- 2022
25. The intestine is a major contributor to circulating succinate in mice
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Wenxin Tong, Sarah A. Hannou, You Wang, Inna Astapova, Ashot Sargsyan, Ruby Monn, Venkataramana Thiriveedi, Diana Li, Jessica R. McCann, John F. Rawls, Jatin Roper, Guo‐fang Zhang, and Mark A. Herman
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Intestines ,Mice ,Citric Acid Cycle ,Succinic Acid ,Genetics ,Animals ,Succinates ,Molecular Biology ,Biochemistry ,Gastrointestinal Microbiome ,Biotechnology - Abstract
The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra- and extracellular metabolic signals regulating pleiotropic biological processes. Despite the importance of circulating TCA cycle metabolites as signaling molecules, the source of circulating TCA cycle intermediates remains uncertain. We observe that in mice, the concentration of TCA cycle intermediates in the portal blood exceeds that in tail blood indicating that the gut is a major contributor to circulating TCA cycle metabolites. With a focus on succinate as a representative of a TCA cycle intermediate with signaling activities and using a combination of gut microbiota depletion mouse models and isotopomer tracing, we demonstrate that intestinal microbiota is not a major contributor to circulating succinate. Moreover, we demonstrate that endogenous succinate production is markedly higher than intestinal succinate absorption in normal physiological conditions. Altogether, these results indicate that endogenous succinate production within the intestinal tissue is a major physiological source of circulating succinate. These results provide a foundation for an investigation into the role of the intestine in regulating circulating TCA cycle metabolites and their potential signaling effects on health and disease.
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- 2022
26. Renal Metabolome in Obese Mice Treated with Empagliflozin Suggests a Reduction in Cellular Respiration
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Surabhi Bangarbale, Blythe D. Shepard, Shivani Bansal, Meth M. Jayatilake, Ryan Kurtz, Moshe Levi, and Carolyn M. Ecelbarger
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Male ,Aspartic Acid ,Flavin Mononucleotide ,Spermidine ,Cell Respiration ,Mice, Obese ,Phosphatidic Acids ,Succinates ,Kidney ,Biochemistry ,Phosphoenolpyruvate ,Mice ,Glucosides ,Sodium-Glucose Transporter 2 ,Metabolome ,Phosphatidylcholines ,Animals ,Urea ,Spermine ,SGLT2 ,gluconeogenesis ,oxidative phosphorylation ,renal ,proximal tubule ,Benzhydryl Compounds ,Sodium-Glucose Transporter 2 Inhibitors ,Uridine ,Molecular Biology - Abstract
Sodium glucose cotransporter, type 2 inhibitors, such as Empagliflozin, are protective of the kidneys by unclear mechanisms. Our aim was to determine how Empagliflozin affected kidney cortical metabolome and lipidome in mice. Adult male TALLYHO mice (prone to obesity) were treated with a high-milk-fat diet, or this diet containing Empagliflozin (0.01%), for 8 weeks. Targeted and untargeted metabolomics and lipidomics were conducted on kidney cortex by liquid chromatography followed by tandem mass-spectroscopy. Metabolites were statistically analyzed by MetaboAnalyst 5.0, LipidSig (lipid species only) and/or CEU Mass Mediator (untargeted annotation). In general, volcano plotting revealed oppositely skewed patterns for targeted metabolites (primarily hydrophilic) and lipids (hydrophobic) in that polar metabolites showed a larger number of decreased species, while non-polar (lipids) had a greater number of increased species (>20% changed and/or raw p-value < 0.05). The top three pathways regulated by Empagliflozin were urea cycle, spermine/spermidine biosynthesis, and aspartate metabolism, with an amino acid network being highly affected, with 14 of 20 classic amino acids down-regulated. Out of 75 changed polar metabolites, only three were up-regulated, i.e., flavin mononucleotide (FMN), uridine, and ureidosuccinic acid. Both FMN and uridine have been shown to be protective of the kidney. Scrutiny of metabolites of glycolysis/gluconeogenesis/Krebs cycle revealed a 20–45% reduction in several species, including phosphoenolpyruvate (PEP), succinate, and malic acid. In contrast, although overall lipid quantity was not higher, several lipid species were increased by EMPA, including those of the classes, phosphatidic acids, phosphatidylcholines, and carnitines. Overall, these analyses suggest a protection from extensive metabolic load and the corresponding oxidative stress with EMPA in kidney. This may be in response to reduced energy demands of the proximal tubule as a result of inhibition of transport and/or differences in metabolic pools available for metabolism.
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- 2022
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27. Practical spectrophotometric assay for the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase, a potential antibiotic target.
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Heath, Tahirah K., Jr.Lutz, Marlon R., Reidl, Cory T., Guzman, Estefany R., Herbert, Claire A., Nocek, Boguslaw P., Holz, Richard C., Olsen, Kenneth W., Ballicora, Miguel A., and Becker, Daniel P.
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SUCCINATES , *BACTERIAL enzymes , *SPECTROPHOTOMETRY , *ANTIBIOTICS , *TARGETED drug delivery , *GLUTAMIC acid - Abstract
A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I)(COD)(S,S)-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE) including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics. [ABSTRACT FROM AUTHOR]
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- 2018
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28. LY2405319, an analog of fibroblast growth factor 21 ameliorates α-smooth muscle actin production through inhibition of the succinate—G-protein couple receptor 91 (GPR91) pathway in mice.
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Le, Cong Thuc, Nguyen, Giang, Park, So Young, Choi, Dae Hee, and Cho, Eun-Hee
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HEPATIC fibrosis , *FIBROBLAST growth factors , *SUCCINATES , *G protein coupled receptors , *ANIMAL models in research , *THERAPEUTICS - Abstract
Fibroblast growth factor 21 (FGF21) is an important metabolic regulator expressed predominantly in the liver. In this study, we evaluated the role of LY2405319, an analogue of FGF21, in hepatic stellate cell (HSC) activation and in a methionine and choline-deficient (MCD)-diet induced mouse model of liver fibrosis. During liver injury, HSCs trans-differentiate into activated myofibroblasts which produce alpha-smooth muscle actin (α-SMA) and become a major cell type in hepatic fibrogenesis. Succinate and succinate receptor (GPR91) signaling has emerged as a regulator to promote α-SMA production in MCD diet- induced mice. Treatment with palmitate or MCD medium on LX-2 cells (HSCs) increased succinate concentration in the conditioned medium and cell lysate of LX-2 cells and increased production of GPR91 and α-SMA. However, LY2405319 administration ameliorates palmitate or MCD media-induced succinate production and decreases over-expression of GPR91 and α-SMA in LX2-cells. In an in vivo study, the MCD diet treatment caused increased steatohepatitis and liver fibrosis compared with the control diet in mice. Administration of LY2405319 improved steatohepatitis ameliorated GPR91 and α -SMA production in the liver, decreased succinate concentration in both liver and serum of MCD diet -induced mice. These results suggest that FGF21 reduces production of α-SMA by inhibiting the succinate-GPR91 pathway. We conclude that FGF21 acts as an inhibitor of the succinate-GPR91 pathway to control liver fibrosis. This suggests that FGF21 has therapeutic potential for treating liver fibrogenesis. [ABSTRACT FROM AUTHOR]
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- 2018
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29. Prediction of reaction knockouts to maximize succinate production by Actinobacillus succinogenes.
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Nag, Ambarish, St. John, Peter C., Crowley, Michael F., and Bomble, Yannick J.
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SUCCINATES , *ACTINOBACILLUS , *GRAM-negative bacteria , *METABOLIC flux analysis , *BIOSYNTHESIS , *BIOENGINEERING - Abstract
Succinate is a precursor of multiple commodity chemicals and bio-based succinate production is an active area of industrial bioengineering research. One of the most important microbial strains for bio-based production of succinate is the capnophilic gram-negative bacterium Actinobacillus succinogenes, which naturally produces succinate by a mixed-acid fermentative pathway. To engineer A. succinogenes to improve succinate yields during mixed acid fermentation, it is important to have a detailed understanding of the metabolic flux distribution in A. succinogenes when grown in suitable media. To this end, we have developed a detailed stoichiometric model of the A. succinogenes central metabolism that includes the biosynthetic pathways for the main components of biomass—namely glycogen, amino acids, DNA, RNA, lipids and UDP-N-Acetyl-α-D-glucosamine. We have validated our model by comparing model predictions generated via flux balance analysis with experimental results on mixed acid fermentation. Moreover, we have used the model to predict single and double reaction knockouts to maximize succinate production while maintaining growth viability. According to our model, succinate production can be maximized by knocking out either of the reactions catalyzed by the PTA (phosphate acetyltransferase) and ACK (acetyl kinase) enzymes, whereas the double knockouts of PEPCK (phosphoenolpyruvate carboxykinase) and PTA or PEPCK and ACK enzymes are the most effective in increasing succinate production. [ABSTRACT FROM AUTHOR]
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- 2018
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30. Docosahexaenoic Acid Alleviates Brain Damage by Promoting Mitophagy in Mice with Ischaemic Stroke
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Eryi Sun, Jing Zhang, Yan Deng, Jun Wang, Qi Wu, Wei Chen, Xiaodong Ma, Siyuan Chen, Xin Xiang, Yujie Chen, Tairong Wu, Yang Yang, and Bo Chen
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Dynamins ,Aging ,Article Subject ,Docosahexaenoic Acids ,Ubiquitin-Protein Ligases ,Mitophagy ,Brain ,Succinates ,Cell Biology ,General Medicine ,Biochemistry ,Brain Ischemia ,Rats ,Oxygen ,Stroke ,Mice ,Adenosine Triphosphate ,Glucose ,Neuroprotective Agents ,Glutamates ,Brain Injuries ,Animals ,Reactive Oxygen Species ,Protein Kinases ,Ischemic Stroke - Abstract
Mitophagy, the selective removal of damaged mitochondria through autophagy, is crucial for mitochondrial turnover and quality control. Docosahexaenoic acid (DHA), an essential omega-3 fatty acid, protects mitochondria in various diseases. This study aimed to investigate the neuroprotective role of DHA in ischaemic stroke models in vitro and in vivo and its involvement in mitophagy and mitochondrial dysfunction. A mouse model of ischaemic stroke was established through middle cerebral artery occlusion (MCAO). To simulate ischaemic stroke in vitro, PC12 cells were subjected to oxygen–glucose deprivation (OGD). Immunofluorescence analysis, western blotting (WB), electron microscopy (EM), functional behavioural tests, and Seahorse assay were used for analysis. DHA treatment significantly alleviated the brain infarction volume, neuronal apoptosis, and behavioural dysfunction in mice with ischaemic stroke. In addition, DHA enhanced mitophagy by significantly increasing the number of autophagosomes and LC3-positive mitochondria in neurons. The Seahorse assay revealed that DHA increased glutamate and succinate metabolism in neurons after ischaemic stroke. JC-1 and MitoSox staining, and evaluation of ATP levels indicated that DHA-induced mitophagy alleviated reactive oxygen species (ROS) accumulation and mitochondrial injury. Mechanistically, DHA improved mitochondrial dynamics by increasing the expression of dynamin-related protein 1 (Drp1), LC3, and the mitophagy clearance protein Pink1/Parkin. Mdivi-1, a specific mitophagy inhibitor, abrogated the neuroprotective effects of DHA, indicating that DHA protected neurons by enhancing mitophagy. Therefore, DHA can protect against neuronal apoptosis after stroke by clearing the damaged mitochondria through Pink1/Parkin-mediated mitophagy and by alleviating mitochondrial dysfunction.
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- 2022
31. Three New Compounds from Delphinium kamaonense Hunth and Their in Vitro Cytotoxic and Potential Antioxidant Activities
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Chang Gong, Guangxin Zhou, Di Jing, Huijie Song, Jixuan Xu, and Dali Meng
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Magnetic Resonance Spectroscopy ,Molecular Structure ,Molecular Medicine ,Antineoplastic Agents ,Succinates ,Bioengineering ,General Chemistry ,General Medicine ,Delphinium ,Molecular Biology ,Biochemistry ,Antioxidants - Abstract
A new amide (1), two new phenylpropanoid derivatives (2, 3), along with three new natural products, including three nitrogen chirality compounds, N-(3-methoxy-1,3-dioxopropyl)-D-phenylalanine methyl ester (4), N-(3-methoxy-1,3-dioxopropyl)-L-phenylalanine methyl ester (5), and N-acetyl-L-phenylalanine methyl ester (6), as well as dimethyl (2R,3R)-2-hydroxy-3-(((E)-3-(4-hydroxyphenyl)acryloyl)oxy)succinate (7) and dimethyl (S,E)-2-((3-(4-hydroxy-3-methoxyphenyl)acryloyl)oxy)succinate (8) were isolated from Delphinium kamaonense Hunth. Their structures were elucidated by extensive analysis of 1D and 2D NMR, and HR-ESI-MS experiments, and the absolute configurations were determined by comparative analysis of specific optical rotation. Compound 1 exhibited a moderate cytotoxicity effect against Hep-3B cancer cell lines (IC
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- 2022
32. Dioxin-elicited decrease in cobalamin redirects propionyl-CoA metabolism to the β-oxidation-like pathway resulting in acrylyl-CoA conjugate buildup
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Karina Orlowska, Russ R. Fling, Rance Nault, Warren J. Sink, Anthony L. Schilmiller, and Tim Zacharewski
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Polychlorinated Dibenzodioxins ,Aconitic Acid ,Methylmalonyl-CoA Mutase ,Succinates ,Vitamin B 12 Deficiency ,Cell Biology ,Cobalt ,Biochemistry ,Fatty Liver ,Mice ,Vitamin B 12 ,Liver ,Receptors, Aryl Hydrocarbon ,Animals ,Humans ,Environmental Pollutants ,Acyl Coenzyme A ,Cysteine ,Molecular Biology - Abstract
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant that induces diverse biological and toxic effects, including reprogramming intermediate metabolism, mediated by the aryl hydrocarbon receptor. However, the specific reprogramming effects of TCDD are unclear. Here, we performed targeted LC-MS analysis of hepatic extracts from mice gavaged with TCDD. We detected an increase in S-(2-carboxyethyl)-L-cysteine, a conjugate from the spontaneous reaction between the cysteine sulfhydryl group and highly reactive acrylyl-CoA, an intermediate in the cobalamin (Cbl)-independent β-oxidation-like metabolism of propionyl-CoA. TCDD repressed genes in both the canonical Cbl-dependent carboxylase and the alternate Cbl-independent β-oxidation-like pathways as well as inhibited methylmalonyl-CoA mutase (MUT) at lower doses. Moreover, TCDD decreased serum Cbl levels and hepatic cobalt levels while eliciting negligible effects on gene expression associated with Cbl absorption, transport, trafficking, or derivatization to 5'-deoxy-adenosylcobalamin (AdoCbl), the required MUT cofactor. Additionally, TCDD induced the gene encoding aconitate decarboxylase 1 (Acod1), the enzyme responsible for decarboxylation of cis-aconitate to itaconate, and dose-dependently increased itaconate levels in hepatic extracts. Our results indicate MUT inhibition is consistent with itaconate activation to itaconyl-CoA, a MUT suicide inactivator that forms an adduct with adenosylcobalamin. This adduct in turn inhibits MUT activity and reduces Cbl levels. Collectively, these results suggest the decrease in MUT activity is due to Cbl depletion following TCDD treatment, which redirects propionyl-CoA metabolism to the alternate Cbl-independent β-oxidation-like pathway. The resulting hepatic accumulation of acrylyl-CoA likely contributes to TCDD-elicited hepatotoxicity and the multihit progression of steatosis to steatohepatitis with fibrosis.
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- 2022
33. Reprint of: Ubisemiquinone Is the Electron Donor for Superoxide Formation by Complex III of Heart Mitochondria
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JULIO F. TURRENS, ADOLFO ALEXANDRE, and ALBERT L. LEHNINGER
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Ubiquinone ,Biophysics ,Succinic Acid ,Antimycin A ,Cytochromes c ,Electrons ,Succinates ,Hydrogen Peroxide ,Cytochromes b ,Biochemistry ,Mitochondria, Heart ,Rats ,Electron Transport ,Electron Transport Complex III ,Reducing Agents ,Superoxides ,Animals ,Molecular Biology ,Oxidation-Reduction - Abstract
Much evidence indicates that superoxide is generated from O
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- 2022
34. Respiratory substrate preferences in mitochondria isolated from different tissues of three fish species
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Jing Long, Yiguo Xia, Hanxun Qiu, Xiaojun Xie, and Yulian Yan
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Oxygen Consumption ,Respiratory Rate ,Physiology ,Animals ,Heart ,Succinates ,General Medicine ,Aquatic Science ,Biochemistry ,Mitochondria - Abstract
Energy requirements of tissues vary greatly and exhibit different mitochondrial respiratory activities with variable participation of both substrates and oxidative phosphorylation. The present study aimed to (1) compare the substrate preferences of mitochondria from different tissues and fish species with different ecological characteristics, (2) identify an appropriate substrate for comparing metabolism by mitochondria from different tissues and species, and (3) explore the relationship between mitochondrial metabolism mechanisms and ecological energetic strategies. Respiration rates and cytochrome c oxidase (CCO) activities of mitochondria isolated from heart, brain, kidney, and other tissues from Silurus meridionalis, Carassius auratus, and Megalobrama amblycephala were measured using succinate (complex II-linked substrate), pyruvate (complex I-linked), glutamate (complex I-linked), or combinations. Mitochondria from all tissues and species exhibited substrate preferences. Mitochondria exhibited greater coupling efficiencies and lower leakage rates using either complex I-linked substrates, whereas an opposite trend was observed for succinate (complex II-linked). Furthermore, maximum mitochondrial respiration rates were higher with the substrate combinations than with individual substrates; therefore, state III respiration rates measured with substrate combinations could be effective indicators of maximum mitochondrial metabolic capacity. Regardless of fish species, both state III respiration rates and CCO activities were the highest in heart mitochondria, followed by red muscle mitochondria. However, differences in substrate preferences were not associated with species feeding habit. The maximum respiration rates of heart mitochondria with substrate combinations could indicate differences in locomotor performances, with higher metabolic rates being associated with greater capacity for sustained swimming.
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- 2022
35. Effects of beeswax emulsified by octenyl succinate starch on the structure and physicochemical properties of acid-modified starchfilms
- Author
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Ruiping Liu, Rui Zhang, Xiaosong Zhai, Cheng Li, Hanxue Hou, and Wentao Wang
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X-Ray Diffraction ,Structural Biology ,Tensile Strength ,Waxes ,Spectroscopy, Fourier Transform Infrared ,Water ,Starch ,Succinates ,General Medicine ,Molecular Biology ,Biochemistry - Abstract
This work aimed to develop a novel strategy to modulate the distribution of beeswax in acid-modified starch films via tuning octenyl succinate starch (OSS) ratios and to elucidate their structure-property relationships. The apparent viscosity and storage modulus of the film-forming solution decreased with the increase of OSS ratio. Attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy revealed that the hydrogen bond in the film-forming network was cleaved with the presence of OSS. Scanning electron microscope (SEM), atomic force microscope (AFM), and X-ray diffraction (XRD) demonstrated that OSS ratio had an obvious effect on the formation and distribution of beeswax crystal particles. Uniform distribution of beeswax effectively enhanced the hydrophobicity and water barrier properties of films and performed preferable elongation at break but at the expense of tensile strength and optical properties. The films with higher OSS ratio (12 %) presented higher thermal stability. This study provides new information on the rational design of emulsified films to obtain desirable physicochemical properties by tuning the distribution of beeswax.
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- 2022
36. Exploring the evolutionary roots and physiological function of itaconate
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Christian M. Metallo and Thekla Cordes
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0106 biological sciences ,Cell ,Biomedical Engineering ,Bioengineering ,Biology ,01 natural sciences ,03 medical and health sciences ,Disease susceptibility ,010608 biotechnology ,medicine ,Animals ,Humans ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Physiological function ,Succinates ,Metabolism ,Small molecule ,Metabolic pathway ,medicine.anatomical_structure ,Enzyme ,chemistry ,Biochemistry ,Metabolic Networks and Pathways ,Function (biology) ,Biotechnology - Abstract
New small molecules are continuing to emerge as metabolically derived regulators of cell function. Itaconate is a recent example where endogenous mammalian synthesis was demonstrated only seven years ago. Since then, interest in the biochemistry and therapeutic potential of itaconate has grown dramatically. Itaconate is an unsaturated dicarboxylic acid that has antimicrobial properties and modulates metabolic pathways throughout the cell. Naturally occurring mutations of enzymes involved in human itaconate synthesis and degradation pathways are associated with disease susceptibility and immunity. Here, we highlight recent discoveries on itaconate metabolism and discuss the relevance of its evolutionary origin to its function in mammals. We also consider the therapeutic relevance of itaconate metabolism and its derivatives for treating metabolic and inflammatory diseases.
- Published
- 2021
37. Correction of mitochondrial dysfunction by succinic acid derivatives under experimental cerebral ischemia conditions
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Denis S. Zolotych, Michael V. Larsky, and Dmitry I. Pozdnyakov
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0301 basic medicine ,Pharmacology ,business.industry ,Ischemia ,General Medicine ,medicine.disease ,Biochemistry ,cerebral ischemia ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Succinic acid ,mitochondrial dysfunction ,succinates ,Medicine ,sense organs ,skin and connective tissue diseases ,business ,Molecular Biology ,030217 neurology & neurosurgery - Abstract
The aim of the study. To evaluate the effect of succinic acid derivatives on changes of mitochondrial function in rats under cerebral ischemia conditions. Materials and methods. In this work, the effect of succinic acid, ethylmethylhydroxypyridine succinate, and acetylaminosuccinic acid at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg (per os) on the change of the neuronal mitochondria function was studied. Cerebral ischemia was reproduced by the Tamura method. The following parameters were evaluated: changes in aerobic/anaerobic metabolism, mitochondrial membrane potential, the opening rate of the mitochondrial pore of transitional permeability and the activity of apoptotic systems. Results. During the study, it was found that the use of the test-compounds at doses of 100 mg/kg and 200 mg/kg contributed to an increase in ATP-generating activity, as well as the maximum respiration level and respiratory capacity, while accompanied by a decrease in the intensity of anaerobic metabolism reactions. Also, upon administration of the test succinic acid derivatives, an increase in the mitochondrial membrane potential and latent opening time of the mitochondrial pore transitional permeability were observed. Moreover, the activity of caspase-3 and apoptosis-inducing factor on groups treated by test objects at doses of 100 mg/kg and 200 mg/kg was significantly lower than that in untreated animals. Conclusion. The studied succinic acid derivatives contribute to the restoration of mitochondrial function in cerebral ischemia conditions, while the most effective dose can be considered to be 100 mg/kg.
- Published
- 2021
38. Characterization of JEN family carboxylate transporters from the acid‐tolerant yeast Pichia kudriavzevii and their applications in succinic acid production
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Yongyan Xi, Tao Zhan, Changhao Bi, Hongtao Xu, Xueli Zhang, Jing Chen, and Feiyu Fan
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Saccharomyces cerevisiae ,Succinic Acid ,Bioengineering ,Applied Microbiology and Biotechnology ,Biochemistry ,Tricarboxylate ,Pichia ,03 medical and health sciences ,chemistry.chemical_compound ,Carboxylic acid transport ,Research Articles ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,biology ,030306 microbiology ,Membrane Transport Proteins ,Succinates ,Tricarboxylic acid ,biology.organism_classification ,Yeast ,chemistry ,Succinic acid ,Fermentation ,TP248.13-248.65 ,Research Article ,Biotechnology ,Organic acid - Abstract
Summary The unconventional yeast Pichia kudriavzevii is renowned for its ability to survive at low pH and has been exploited for the industrial production of various organic acids, especially succinic acid (SA). However, P. kudriavzevii can also utilize the di‐ and tricarboxylate intermediates of the Krebs cycle as the sole carbon sources for cell growth, which may adversely affect the extracellular accumulation of SA. Because the carboxylic acid transport machinery of P. kudriavzevii remains poorly understood, here, we focused on studying its SA transportation process from the perspective of mining and characterization of dicarboxylate transporters in a newly isolated acid‐tolerant P. kudriavzevii strain CY902. Through genome sequencing and transcriptome analysis, two JEN family carboxylate transporters (PkJEN2‐1 and PkJEN2‐2) were found to be involved in SA transport. Substrate specificity analysis revealed that both PkJEN proteins are active dicarboxylate transporters, that can effectively import succinate, fumarate and L‐malate into the cell. In addition, PkJEN2‐1 can transport α‐ketoglutarate, while PkJEN2‐2 cannot. Since PkJEN2‐1 shows higher transcript abundance than PkJEN2‐2, its role in dicarboxylate transport is more important than PkJEN2‐2. In addition, PKJEN2‐2 is also responsible for the uptake of citrate. To our best knowledge, this is the first study to show that a JEN2 subfamily transporter is involved in tricarboxylate transport in yeast. A combination of model‐based structure analysis and rational mutagenesis further proved that amino acid residues 392‐403 of the tenth transmembrane span (TMS‐X) of PkJEN2‐2 play an important role in determining the specificity of the tricarboxylate substrate. Moreover, these two PkJEN transporters only exhibited inward transport activity for SA, and simultaneous inactivation of both PkJEN transporters reduced the SA influx, resulting in enhanced extracellular accumulation of SA in the late stage of fermentation. This work provides useful information on the mechanism of di‐/tricarboxylic acid utilization in P. kudriavzevii, which will help improve the organic acid production performance of this microbial chassis., Two JEN2 transporters responsible for the utilization of dicarboxylic acids in P. kudriavzevii were identified and functionally characterized. The PkJEN2‐2 transporter also possesses specific tricarboxylic acid transportation activity. Inactivation of PkJEN transporters can be used as a useful strategy to increase SA titer in P. kudriavzevii.
- Published
- 2021
39. Dibenzyl-(1S*,2S*)-2,3-dihydro-1H-indene-1,2-dicarboxylate
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Carla CARFAGNA, Diego Olivieri, and RICCARDO TARRONI
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succinic acid ester ,Organic Chemistry ,succinates ,homogeneous catalysis ,carbonylation ,bis-alkoxycarbonylation ,palladium ,aryl a-diimine ligand ,Physical and Theoretical Chemistry ,Biochemistry - Abstract
The synthesis of dibenzyl-(1S*,2S*)-2,3-dihydro-1H-indene-1,2-dicarboxylate has been realized through a diastereospecific bis-alkoxycarbonylation reaction, which starts from the cheap and easily available 1H-indene, benzyl alcohol, and carbon monoxide. The catalyst is formed in situ by mixing Pd(TFA)2, the ligand N2,N3-bis(2,6-dimethylphenyl)butane-2,3-diimine, p-benzoquinone is used as an oxidant, and benzyl alcohol acts both as a nucleophile and as the main solvent.
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- 2023
40. Chemical modification of pullulan exopolysaccharide by octenyl succinic anhydride: Optimization, physicochemical, structural and functional properties
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Mohammad Mousavi, John F. Kennedy, Seyed Saeid Hosseini, Maedeh Omar-Aziz, Faramarz Khodaiyan, Mohammad Saeid Yarmand, and Mohammad Gharaghani
- Subjects
Succinic Anhydrides ,Chemical Phenomena ,02 engineering and technology ,Biochemistry ,Surface tension ,Structure-Activity Relationship ,03 medical and health sciences ,Viscosity ,chemistry.chemical_compound ,Polysaccharides ,Structural Biology ,Particle Size ,Glucans ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Esterification ,Chemistry ,Spectrum Analysis ,Thermal decomposition ,Succinic anhydride ,Chemical modification ,Succinates ,Pullulan ,General Medicine ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Grafting ,Chemical engineering ,Thermogravimetry ,Particle size ,0210 nano-technology - Abstract
Pullulan (PU) is an exo-polysaccharide used in the food and pharmaceutical industries. However, the use of PU in different industries is limited due to its highly hydrophilic nature and consequently weakness in surface properties which can be remedied by its chemical modification with octenyl succinic anhydride (OSA). For this purpose, PU modification with OSA was optimized and the results showed that the maximum degree of substitution (0.061 ± 0.003) was obtained under pH of 9.0, pullulan concentration of 40% (w/w), temperature of ~40.90 °C, reaction time of ~101.21 min and OSA concentration of 14.96% (w/w). Also, the grafting of OSA on pullulan structure was confirmed by FTIR, 1H NMR and zeta-potential analyzes. Although this modification had no significant effect on the amorphousity of pullulan, it led to an increase in viscosity and a decrease in decomposition temperature and surface tension. Improvement of emulsifying properties of PU-OSA sample was proved by the evaluation of emulsifying capacity of un- and modified samples and also, zeta-potential, particle size and viscosity of the prepared emulsions. In line with surface characteristic results, an increase in foam capacity of modified samples was observed with decreasing the interfacial tension.
- Published
- 2020
41. Production of starch-polyester bio-support for lipases immobilization: synergistic action of itaconic acid and nanoclay
- Author
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Bruno Matheus Simões, Michael da Conceição de Castro, Patrícia Salomão Garcia, Tatiane Larissa da Silva Farias, Alessandra Machado Baron, Milena Martins Andrade, Maria Victória Eiras Grossmann, and Debora Aparecida de Almeida
- Subjects
0106 biological sciences ,Immobilized enzyme ,Starch ,Polyesters ,Sodium ,chemistry.chemical_element ,Burkholderia cepacia ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Bacterial Proteins ,010608 biotechnology ,mental disorders ,Organic chemistry ,Itaconic acid ,010405 organic chemistry ,Succinates ,Lipase ,General Medicine ,Enzymes, Immobilized ,Biodegradable polymer ,0104 chemical sciences ,Polyester ,Montmorillonite ,chemistry ,Bentonite ,Biotechnology - Abstract
The objective of the present work was to develop biodegradable polymeric films (starch-PBAT) as support for the immobilization of lipases using sodium montmorillonite (MMT) as a reinforcing agent (...
- Published
- 2020
42. Itaconate regulates the glycolysis/pentose phosphate pathway transition to maintain boar sperm linear motility by regulating redox homeostasis
- Author
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Bo Cheng, Zhendong Zhu, Takashi Umehara, Masaaki Goto, Masayuki Shimada, Wenxian Zeng, Tomoko Kawai, and Natsumi Tsujita
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Male ,0301 basic medicine ,endocrine system ,Swine ,Motility ,Dehydrogenase ,Oxidative phosphorylation ,Carbohydrate metabolism ,Pentose phosphate pathway ,Biochemistry ,Pentose Phosphate Pathway ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Animals ,Homeostasis ,Glycolysis ,urogenital system ,Chemistry ,Succinates ,Metabolism ,Spermatozoa ,Sperm ,Cell biology ,Glucose ,030104 developmental biology ,Oxidation-Reduction ,030217 neurology & neurosurgery - Abstract
Mammalian cells improve redox homeostasis under reactive oxygen species (ROS) stress conditions via the enhancement of the pentose phosphate pathway (PPP). However, it is not clear how the cell reprograms glucose metabolism from glycolysis to the PPP. Hence, in the present study, we used boar sperm as a model to elucidate the mechanism by which the glycolysis/PPP transition occurs under ROS stress. The boar sperm treated with moderate glucose levels for 3 h exhibited increased sperm linear motility patterns, ATP levels and GSH/GSSG ratios and decreased ROS levels compared to the boar sperm treated without glucose. In addition, the hexokinase activity, glucose-6-phosphate dehydrogenase (G6PD) activity, NADPH level, NADPH/NADP+ ratio and mitochondrial activity were higher in the sperm treated with moderate glucose than in those not treated with glucose. Interestingly, the enzyme activity of fructose-1,6-bisphosphate aldolase (ALDOA) was not significantly changed during the incubation. The sperm linear motility patterns were decreased by treatment with the G6PD inhibitor 6-aminonicotinamide. Moreover, moderate glucose treatment significantly increased the itaconate levels in sperm. Both endogenous and exogenous itaconate increased the total itaconate modifications and the itaconate-modified ALDOA levels in sperm, suggesting that under moderate-glucose conditions, glycolysis in the sperm was suppressed by an increase in the itaconate levels. Furthermore, the addition of itaconate improved the sperm linear motility patterns by suppressing glycolysis and enhancing oxidative phosphorylation (OXPHOS). Therefore, the itaconate generated from OXPHOS regulates the glycolysis/PPP transition to maintain redox homeostasis. In sperm, this itaconate-dependent mechanism plays an important role in maintaining their high linear motility.
- Published
- 2020
43. Chiral Assembly and Recognition of Seven Copper (II) Coordination Polymers from Tartaric Acid Derivative Ligands
- Author
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Zong‐Ying Li, Bin Yuan, Hai‐Xian Wang, Tian‐Sheng He, Yan‐Long Lan, Si‐Yu Wang, Li‐Na Zhu, DeMing Kong, and Xiao‐Zeng Li
- Subjects
Polymers ,Organic Chemistry ,Succinates ,General Chemistry ,Crystallography, X-Ray ,Ligands ,Tartrates ,Biochemistry ,Copper - Abstract
A pair of enantiomeric ligands, (2R,3R)-dibenzyl-2,3-bis(isonicotinoyloxy)succinate ((R,R)-L) and (2S,3S)-dibenzyl-2,3-bis(isonicotinoyloxy)succinate ((S,S)-L), are designed and synthesized. Seven copper (II) coordination polymers {[Cu((R,R)-L)Br
- Published
- 2022
44. Tailoring key enzymes for renewable and high-level itaconic acid production using genetic Escherichia coli via whole-cell bioconversion
- Author
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Chuan-Chieh Hsiang, Priskila Adjani Diankristanti, Shih-I. Tan, Yi-Chia Ke, Yeong-Chang Chen, Sefli Sri Wahyu Effendi, and I-Son Ng
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Aspergillus ,Fermentation ,Escherichia coli ,Bioengineering ,Succinates ,Applied Microbiology and Biotechnology ,Biochemistry ,Biotechnology - Abstract
Renewable chemical productions through carbon-neutral design are widely concerned in recent years. Among all, itaconic acid (IA) is one of the most important building block chemicals from biorefinery. However, IA fermentation by the eukaryotic Aspergillus terreus is time-consuming and less productive. The whole-cell (WC) bioconversion, proposed as an alternative approach by transforming citrate into IA via two key enzymes of aconitase (ACN, EC 4.2.1.3) and cis-aconitate decarboxylase (CAD, EC 4.1.1.6), is attractive. In this study, we screened the best genes from genes library, studied the kinetics parameters of ACN from Corynebacterium glutamicum (Cg) and CAD from Aspergillus terreus (At), thus achieving the maximum IA production. The catalytic activity of CgAcnA was 39-fold of AtCadA, indicating CAD was the rate-determining step. For metal ions effect, copper and ferric ions inhibited 95% and 59% enzyme activity when both enzymes co-worked together. Finally, the engineered Escherichia coli expressing dual genes and cultured in glycerol-included medium reached the highest IA titer of 67 g/L and productivity of 8.375 g/L/h, which demonstrates as a promising renewable process.
- Published
- 2022
45. Graphene oxide incorporated chitosan/acrylamide/itaconic acid semi-interpenetrating network hydrogel bio-adsorbents for highly efficient and selective removal of cationic dyes
- Author
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Yasemin Tamer, Alper Koşucu, and Hale Berber
- Subjects
Acrylamide ,Chitosan ,Nanogels ,Hydrogels ,Succinates ,General Medicine ,Biochemistry ,Water Purification ,Methylene Blue ,Kinetics ,Structural Biology ,Graphite ,Adsorption ,Coloring Agents ,Molecular Biology ,Water Pollutants, Chemical - Abstract
In recent years, polymeric bio-adsorbents offers high removal efficiency, superior adsorption capacity and selectivity against various pollutants in aqueous medium. While designing these adsorbents, their environmental friendliness, sustainability, renewability, easy accessibility, and cost-effectiveness should be considered. In this study, GO incorporated semi-interpenetrating network (semi-IPN) nanocomposite hydrogels (CS/AAm/IA/GO) were obtained by free radical copolymerization of acrylamide (AAm) and itaconic acid (IA) in the presence of chitosan (CS) as an environmentally friendly bio-adsorbent. GO significantly improved the thermal stability, compressive strength, and percentage swelling of the hydrogel. The selective adsorption studies demonstrated that methylene blue (MB) was the most efficiently removed dye from both individual and mixed dye systems with 99.8 % removal efficiency. The adsorption capacity was found to be 247.47 mg g
- Published
- 2022
46. ß-Hydroxybutyrate Improves Mitochondrial Function After Transient Ischemia in the Mouse
- Author
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Alina Lehto, Konrad Koch, Johanna Barnstorf-Brandes, Christian Viel, Marius Fuchs, and Jochen Klein
- Subjects
3-Hydroxybutyric Acid ,Hydroxybutyrates ,Neurodegenerative Diseases ,Succinates ,General Medicine ,Ketone Bodies ,Biochemistry ,Mitochondria ,Cellular and Molecular Neuroscience ,Mice ,Neuroprotective Agents ,Ischemia ,Animals ,Citrates - Abstract
ß-Hydroxybutyrate (BHB) is a ketone body formed in high amounts during lipolysis and fasting. Ketone bodies and the ketogenic diet were suggested as neuroprotective agents in neurodegenerative disease. In the present work, we induced transient ischemia in mouse brain by unilaterally occluding the middle cerebral artery for 90 min. BHB (30 mg/kg), given immediately after reperfusion, significantly improved the neurological score determined after 24 h. In isolated mitochondria from mouse brain, oxygen consumption by the complexes I, II and IV was reduced immediately after ischemia but recovered slowly over 1 week. The single acute BHB administration after reperfusion improved complex I and II activity after 24 h while no significant effects were seen at later time points. After 24 h, plasma and brain BHB concentrations were strongly increased while mitochondrial intermediates (citrate, succinate) were unchanged in brain tissue. Our data suggest that a single administration of BHB may improve mitochondrial respiration for 1–2 days but not for later time points. Endogenous BHB formation seems to complement the effects of exogenous BHB administration.
- Published
- 2022
47. Short-chain fatty acid metabolism and multiple effects on cardiovascular diseases
- Author
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Tongtong Hu, Qingqing Wu, Qi Yao, Kebing Jiang, Jiabin Yu, and Qizhu Tang
- Subjects
Heart Failure ,Aging ,Succinates ,Atherosclerosis ,Fatty Acids, Volatile ,Biochemistry ,Malonates ,Receptors, G-Protein-Coupled ,Butyrates ,Neurology ,Cardiovascular Diseases ,Hypertension ,Humans ,Propionates ,Reactive Oxygen Species ,Molecular Biology ,Biotechnology - Abstract
Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, and fatty acid metabolism has been well studied. Short-chain fatty acids (SCFAs) have been less discussed than long-chain fatty acids (LCFAs) in CVDs. However, increasing evidence indicates the importance of SCFAs in regulating cardiac function. Here, we summarize the current understanding of SCFAs in hypertension, ischaemic reperfusion, myocardial infarction, atherosclerosis and heart failure. Most SCFAs exert positive effects in regulating related diseases. Butyrate and propionate can reduce blood pressure, improve I/R injury and decrease the risk of coronary artery disease (CAD) and atherosclerosis. Acetate can also play a positive role in regulating hypertension and preventing atherosclerosis, and malonate can improve cardiac function after MI. They affect these diseases by regulating inflammation, the immune system and related G protein-coupled receptors, with multiple neurohumoural regulation participation. In contrast, succinate can accelerate IR injury, increasing mitochondrial ROS production. SCFAs ultimately affect the regulation of different pathophysiological processes in heart failure. Here, we clarified the importance of short-chain fatty acids in the cardiovascular system and their multiple effects in various pathophysiological processes, providing new insights into their promising clinical application. More research should be conducted to further elucidate the underlying mechanism and different effects of single or multiple SCFA supplementation on the cardiovascular system.
- Published
- 2022
48. Modular structure of complex II: An evolutionary perspective
- Author
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Valeriya Karavaeva, Filipa L Sousa, and Filipa Sousa
- Subjects
Succinate:Quinone oxidoreductase ,Comparative genomics ,Biophysics ,Succinic Acid ,Succinates ,Fumarate reductase ,Cell Biology ,Quinol:Fumarate reductase ,Biochemistry ,Catalysis ,Succinate dehydrogenase ,Fumarates ,Multienzyme Complexes ,Electron transport chain - Abstract
Succinate dehydrogenases (SDHs) and fumarate reductases (FRDs) catalyse the interconversion of succinate and fumarate, a reaction highly conserved in all domains of life. The current classification of SDH/FRDs is based on the structure of the membrane anchor subunits and their cofactors. It is, however, unknown whether this classification would hold in the context of evolution. In this work, a large-scale comparative genomic analysis of complex II addresses the questions of its taxonomic distribution and phylogeny. Our findings report that for types C, D, and F, structural classification and phylogeny go hand in hand, while for types A, B and E the situation is more complex, highlighting the possibility for their classification into subgroups. Based on these findings, we proposed a revised version of the evolutionary scenario for these enzymes in which a primordial soluble module, corresponding to the cytoplasmatic subunits, would give rise to the current diversity via several independent membrane anchor attachment events.
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- 2022
49. Preparation of imidazolidinone compounds as derivatization reagent for diastereomerization and chromatographic separation of chiral organic acids
- Author
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Maho Umino, Tatsuya Sakamoto, Mayu Onozato, and Takeshi Fukushima
- Subjects
Tandem Mass Spectrometry ,Organic Chemistry ,Carboxylic Acids ,Indicators and Reagents ,Stereoisomerism ,Succinates ,General Medicine ,Lactic Acid ,Biochemistry ,Analytical Chemistry ,Chromatography, Liquid - Abstract
A chiral derivatization reagent for application in LC-tandem mass spectrometry (LC-MS/MS)-based detection, benzyl 5-(2-aminoethyl)-3-methyl-4-oxoimidazolidine-1-carboxylate (CIM-C
- Published
- 2022
50. In-situ reaction compatibilization modification of poly(butylene succinate-co-terephthalate)/polylactide acid blend films by multifunctional epoxy compound
- Author
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Xiangyu Wang, Hongwei Pan, Shiling Jia, Zepeng Wang, Hanlin Tian, Lijing Han, and Huiliang Zhang
- Subjects
Structural Biology ,Polymers ,Polyesters ,Phthalic Acids ,Epoxy Compounds ,Succinates ,General Medicine ,Alkenes ,Molecular Biology ,Biochemistry - Abstract
Poly(butylene succinate-co-terephthalate) (PBST) copolyester, is a new type of biodegradable synthetic polymer material that has emerged in recent years, but it cannot meet the market requirements, because of its low strength. The high-strength and high-modulus polylactic acid (PLA) was blended with PBST to increase its strength, and the chain extender ADR-4370 was used to modify PBST/PLA films by reaction and compatibilization. Compared with the 80/20 wt% PBST/PLA films, the tensile strength after modification with 0.3 wt% ADR was increased by 21.8 % and 44.3 % in the machine direction (MD) and in the transverse direction (TD), respectively. The Water Vapor Permeability (WVP) was decreased from 10.0 × 10
- Published
- 2022
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