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PubMed1982

Comparison of cytosolic and mitochondrial enzyme alterations in the livers of propionic or methylmalonic acidemia: a reduction of cytochrome oxidase activity.

The activities of mitochondrial, cytosolic and microsomal enzymes in liver specimens obtained from three patients with propionic or methylmalonic acidemia were compared with those of control patients who had died from unrelated causes. Only the activity of cytochrome oxidase (mitochondrial enzyme) was significantly reduced in the patients of propionic acidemia and methylmalonic acidemia who were in the state of metabolic acidosis; in two patients the activity was less than 30% of that in controls, but in the other patient of propionic acidemia, who was under the treatment with a low protein diet (0.8 g/kg/day), the activity was 50% of that in controls. The metabolites of branched chain amino acids (tiglic acid, propionic acid, methylmalonic acid, succinic acid, tiglyl-CoA and propionyl CoA) exhibited no inhibitory effect on the cytochrome oxidase activity of the sonicated rat liver mitochondria. The reduction of cytochrome oxidase activity found in these organic acidemias may be caused secondarily by some unknown mechanism.

Amino Acid Metabolism, Inborn Errors↗
PubMed1969

Study on the (14)C-glucose metabolism by Clonorchis sinensis: Paper Chromatographic Analyses in Combination with Autoradiography.

Radioactive (14)C-glucose(U) was given to Clonorchis sinensis in Tris buffer medium, in corder to trace the metabolic fate of the labelled carbon. The labelled carbon from glucose enters into intermediary metabolites and end products of anaeroblic glycolysis, Embden-Meyerhof pathway, and of aerobic Krebs cycle. These product were identified by one or two-dimensional paper chromatography in combination with autoradoigraphy. 1)The labelled metabolites detected in this experiment corresponded to pyruvic acid, latic acid, malic acid, succinic acid and fumaric acid. 2)Amino acids, such as alanine, aspartic acid, glutamic acid, valine, theronine, and serine, derived by the degradation of (14)C- glycose were also found. 3)Labelled compounds behaving like alanine, aspartic acid and glutamic acid were observed in the chroma to gram of incubation medium. 4)The preciptation which suggests a positive reaction for protein occured when absolute ethanol was added to the incubation medium.

Journal Article↗
PubMed2026

Enzyme-Metabolite Network Analysis of Endometrial Cancer-Derived Extracellular Vesicles Through Integrated Proteomics and Metabolomics.

Endometrial cancer (EC) is the most common gynecological malignancy in high-income countries. Extracellular vesicles (EVs) are key mediators of intercellular communication and metabolic reprogramming, but their molecular cargo in EC remains poorly characterized. EVs were isolated from four EC cell lines representing Type I and Type II subtypes (AN3CA, ISHIKAWA, HEC1A, and KLE). Untargeted metabolomics was performed by HILIC-LC-MS/MS, proteomics by data-independent acquisition (DIA) mass spectrometry, and multi-omics integration using MetaboAnalyst and OmicsNet. Metabolomic profiling identified 1463 annotated features and revealed significant differences among EC cell lines (PERMANOVA, p = 0.002). Twenty-eight differentially abundant metabolites, including lactic acid, succinic acid, and uric acid, were identified. Proteomic analysis quantified 8513 proteins with subtype-specific expression patterns. Integrated analysis revealed seven significantly enriched pathways, including glycolysis/gluconeogenesis, central carbon metabolism in cancer, and the pentose phosphate pathway. Increased LDHA abundance in metastatic AN3CA-derived EVs was confirmed by Western blot (p = 0.047). EC-derived EVs display subtype- and metastatic-status-specific metabolo-proteomic signatures, with glycolysis, TCA cycle remodeling, and central carbon metabolism as convergent pathway signatures of molecular reprogramming. These findings establish a multi-omics framework for characterizing EV cargo in EC and identify candidate enzyme-metabolite nodes for future biomarker validation in patient-derived specimens.

Female↗
PubMed2001

[A study of analyzing short-chain fat acid by gradient reversed-phase high-performance liquid chromatography].

OBJECTIVE: The objective of this study is to obtain the optimized separating conditions of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, lactic acid, succinic acid from bacteria using reversed-phase high performance liquid chromatograph (RP-HPLC), and to set up a reliable progress in identifying the end-products of oral bacteria. METHODS: The conditions of separating seven short-chain fat acids were optimized using the method of gradient RP-HPLC. RESULTS: The study showed that the optimal chromatographic parameters were: 1.0 ml/min and 2.0 ml/min of flow rates, and the wavelength of ultraviolet detection was 217 nm. The composition of eluent: the ratio of phosphate buffer (pH 2.8) to methanol is 95:5 (v/v), gradient 5%-50%. The liner gradient wash will be performed in 10 minutes at room temperature. The average recovery rate was 92%, and RSD was 1.8%. CONCLUSION: The results of this paper will be helpful to determine acid composition of end products of oral bacteria.

Chromatography, High Pressure Liquid↗
PubMed2001

[Simultaneous determination of 11 organic acids in fruit juice by ion exclusion chromatography].

A method for the quantitative determination of 11 organic acids (oxalic acid, citric acid, tartaric acid, malic acid, ascorbic acid, lactic acid, succinic acid, formic acid, acetic acid, glutaric acid and fumaric acid) in fruit juice was developed successfully. It was based on an ion exclusion chromatographic separation under the conditions of isocratic elution with 17 mmol/L sulphuric acid solution with the ICE-ION-300 ion exclusion column, and the UV detection at 210 nm. The precision of the method was investigated and the relative standard deviations were from 1.5% to 9.8% (n = 10).

Beverages↗
PubMed1992

[Chemical constituents of the roots of Ostericum grosseserratum (Maxim.) Kitag].

This paper reports the isolation of eleven compounds from the roots of Ostericum grosseserratum, of which nine compounds were elucidated as myristic acid, palmitic acid, stearic acid, octacosanoic acid, succinic acid, beta-sitosterol, sitosterol-beta-D-glucoside, isoscopletin and sucrose. The results are helpful in the study of plant taxonomy.

Drugs, Chinese Herbal↗
PubMed1998

Preliminary investigations in matrix-based tablet formulations of diltiazem hydrochloride containing succinic acid-treated methylcellulose.

The feasibility of using succinic acid-treated methylcellulose in matrix-based tablets of diltiazem hydrochloride was investigated in this study. A 2(3) factorial design was employed to investigate the effect of ratio of methylcellulose to succinic acid, amount of ethyl alcohol, and drying time on the percentage drug dissolved in 300 min. The tablets were prepared by wet granulation technique. The ratio of methylcellulose to succinic acid was found to significantly influence the swelling and gelling characteristics of the polymer. Carbonyl peak was found in the infrared (IR) spectra of the samples modified using succinic acid, suggesting the presence of an ester group. The results of an ANOVA test revealed that the significance of the ratio of methylcellulose to succinic acid and drying time was greater in magnitude than that of amount of alcohol in controlling the drug release in 300 min. The results of F-test revealed that the zero-order model fits well to the in vitro dissolution data. The characteristics of methylcellulose can be changed by reacting it with succinic acid and the resultant product can be used as a hydrophilic matrixing agent.

Calcium Channel Blockers↗
PubMed1973

Biosynthesis of glutamic acid in Saccharomyces: accumulation of tricarboxylic acid cycle intermediates in a glutamate auxotroph.

Aconitaseless glutamic acid auxotroph MO-1-9B of Saccharomyces grew in glutamic acid-supplemented minimal medium, but failed to grow when glutamic acid was substituted by proline, arginine, ornithine, or glutamine. This mutant was also unable to utilize lactate or glycerol as a carbon source. Under a glutamic acid-limiting condition, by using acetate-1-(14)C as tracer, the mutant accumulated rather large amounts of (14)C-citric acid and (14)C-succinic acid when compared with the wild-type strain. Under excess glutamic acid supplementation, accumulation of citric acid and succinic acid was considerably reduced. When (14)C-glutamic acid-(U) was used as tracer, (14)C-alpha-ketoglutaric acid, (14)C-citric acid, and (14)C-succinic acid were accumulated in the mutant. The citric acid peak was the largest, followed by alpha-ketoglutaric acid and succinic acid. In the wild-type strain under similar conditions, only small amounts of (14)C-citric acid and (14)C-succinic acid and no (14)C-alpha-ketoglutaric acid were accumulated.

Acetates↗
PubMed2006

Microenvironmental pH and microviscosity inside pH-controlled matrix tablets: an EPR imaging study.

Incorporation of pH modifiers is a commonly used strategy to enhance the dissolution rate of weakly basic drugs from sustained release solid dosage forms. Electron paramagnetic resonance imaging (EPRI) was applied to spatially monitor pH(M) and the rotational correlation time (tau(R)), a parameter which is closely related to the surrounding microviscosity inside HPMC (hydroxypropylmethylcellulose) matrix tablets. Fumaric, citric, and succinic acid were employed as pH modifiers. 4-(methylamino)-2-ethyl-5,5-dimethyl-4-pyridine-2-yl-2,5-dihydro-1H-imidazole-1-oxyl (MEP) was used as spin label. Fumaric and citric acid reduced the pH(M) to equal extents in the initial phase. With the progress of hydration, the more soluble citric acid diffused out from the tablet resulting in an increase in pH(M), originating at the outer layers. In contrast, fumaric acid maintained a constantly reduced pH(M) inside the entire tablet. Due to its lower acidic strength, succinic acid did not reduce the pH(M) as effectively as the other pH modifiers used. The more water-soluble acids stimulated the water penetration into the matrix system, thereby rapidly decreasing tau(R). Once the matrix tablets were hydrated, the included pH modifiers influenced tau(R) insignificantly. EPRI, a novel approach for monitoring pH(M) and tau(R) non-invasively and spatially resolved, was used successfully for the optimization of an pH-controlled formulation.

Chemistry, Pharmaceutical↗
PubMed2002

Increase of sample load without peak deterioration by careful selection of electrolyte in capillary zone electrophoresis.

In this study it is demonstrated that much higher concentrations of bases dissolved in water can be injected in capillary zone electrophoresis without causing peak deterioration, e.g., peak splitting, if it is the co-ion that buffers instead of the counter-ion. Those findings can be utilised to control peak shapes and in this way an increase in the sample load and indirectly a decrease in the detection limits of impurities in the sample can be obtained. Good results were obtained with 4-aminobutyric and 6-aminocaproic acids as buffering co-ions. Another possibility evaluated successfully was that of using a dibasic acid, malic acid or succinic acid. With an electrolyte containing both succinic acid and 6-aminocaproic acid at pH 4.5, it was possible to load at least 10-20 times more of the test substances imidazole, creatinine or 2-aminopyrimidine dissolved in water than with an electrolyte at the same pH containing acetic acid and tris(hydroxymethyl)aminomethane.

Electrolytes↗
PubMed1981

Urinary excretion of C4--C10-dicarboxylic acids and antiketogenic properties of adipic acid in ketogenic-stimulated rats due to diabetes, long-chain and short-chain monocarboxylic acids.

The urinary excretion of C4--C10-dicarboxylic acids (succinic, adipic, suberic and sebacic acids) and the antiketogenicity of adipic acid have been studied in ketogenic-stimulated rats in three biochemically different states: diabetes, fat-feeding (long-chain monocarboxylic acids) and feeding of hexanoic acid (short-chain monocarboxylic acid). In diabetic rats urinary excretions of adipic and suberic acids were elevated before the rise in urinary excretions of 3-hydroxybutyric acid, i.e. before ketosis appeared. In severe diabetic ketosis sebacic acid was below normal values, whereas the excretion of succinic acid was unaltered. Rats, in which ketosis was provoked by hexanoic acid, had preketotic high urinary excretions of adipic and succinic acids. After ketosis the excretions of succinic acid declined again whereas the excretion of adipic acid rose further, together with that of suberic acid. Moreover, when rats which were ketotic due to treatment with long-chain triacylglycerol or hexanoic acid received 500 mg of adipic acid the urinary excretion of succinic acid rose significantly. However, no changes in succinic acid excretion were seen in diabetic ketotic rats treated with the same amount of adipic acid. Exogenously administered adipic acid was strongly antiketogenic towards ketosis caused by long-chain or short-chain monocarboxylic acids, but had no effect on diabetic ketosis.

Acidosis↗
PubMed1969

Absorption of therapeutic preparations of iron measured with a whole body counter.

The Oxford Whole Body Counter was used to measure absorption from various therapeutic preparations of iron in five groups of subjects. Succinic acid enhanced absorption of iron when added to a solution of ferrous fumarate, but not when given with tablets of ferrous fumarate or ferrous sulphate. Ferrous fumarate plus ascorbic acid was absorbed better than ferrous fumarate alone but no better than ferrous sulphate. The addition of ascorbic acid and succinic acid to tablets of ferrous sulphate did not enhance absorption significantly.

Anemia, Hypochromic↗
PubMed1998

Product yields from irradiated glycylglycine in oxygen-free solutions: Monte Carlo simulations and comparison with experiments.

The radiation chemistry of photon-irradiated aqueous solutions of biological molecules may be considered under four distinct time regimes: physical transport (< or = 10(-15) s); prechemical conversion of H2O+, H2O*, and subexcitation electrons into free radicals and molecular products (10(-15) s to 10(-12) s); chemical reactions within individual electron tracks (10(-12) s to 10(-6) s); and chemical reactions within overlapping tracks (>10(-6) s). We have previously reported of the use of the Monte Carlo radiation transport/chemistry codes OREC and RADLYS to model the radiolysis of glycylglycine in oxygen-free solution to a time of 1 micros. These simulations successfully predicted the yields of free ammonia, an end product created solely in the reaction of the hydrated electron with the solute within individual tracks. Other measurable products are only partially created during intratrack reactions, and thus one must additionally consider the late, intertrack chemistry of this system. In this paper, we extend our simulations of glycylglycine radiolysis to model for the first time the events which occur during this late chemistry stage. The model considers the product rates of the reactants in bulk solution by using previously available microsecond intratrack yields given by single-track OREC/RADLYS simulations and an x-ray dose rate of 2.80 Gy min(-1) as used in a companion experimental program. These rates are then applied in a series of coupled, differential rate equations that describe the solution chemistry of glycylglycine radiolysis. Product yields are reported as a function of time over a total irradiation period of 10(4) s. Excellent overall agreement is seen between the theoretical predictions and measurements of five radiolysis end products: free ammonia, acetylglycine, diaminosuccinic acid, aspartic acid, and succinic acid. The model also gives the explicit contributions of intratrack and intertrack reactions to the various end products. For example, the model predicts that approximately 56% and 93% of succinic acid and aspartic acid, respectively, are produced during intertrack reactions at a solute concentration of 0.05 M; these contributions drop to 0.07% and 11%, respectively, at 1.2 M.

Computer Simulation↗
PubMed2000

Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.

Calcium Channel Blockers↗
PubMed2003

Corrections of prooxidant-antioxidant homeostasis of organism under hypoxia of different genesis by yackton, a new pharmacological preparation.

The aim of the present work was to study the antioxidant activity of the new derivative of succinic acid-succinate mono[(2-dimethyl-amino) ethyl ether] of succinic acid (yackton) under conditions of hypoxic and hemic hypoxia as well as to examine in vitro the antiradical activity of this preparation. Hypoxia in the rats was modelled by: (i) allowing the rats to breath a gas mixture with 7% O2 and 93% N2 for 30 minutes (hypoxic hypoxia), and (ii) injecting the rats sodium nitrite subcutaneously in a dose of 60 mg/kg body weight (hemic hypoxia). Yackton was injected intraperitoneally to both groups 30 minutes before the extreme influence in a dose of 140 mg/kg body weight. Then in homogenates and in post-mitochondrial fractions of liver, heart, lungs, brain we studied the content of secondary products of lipid peroxidation (LPO), activity of antioxidant enzymes superoxide dismutase (SOD) and catalase, and the activity of enzymes responsible for the maintenance of reduced glutathione (GSH) glutathione reductase (GR-ase) and glutathione peroxidase (GP-ase). In vitro studies were made on the antiradical activity of yackton in reaction with the stable radical diphenylpicrylhydrazine (DPPH) as well as on the reaction velocity of the preparation with DPPH, and its period of semi-transformation in a non-radical form. It was shown that yackton treatment before hypoxic and hemic hypoxia decreased lipid peroxidation (LPO) level and increased SOD activity. After the yackton injection the state of glutathione system was normalized in comparison with its state at hypoxic and hemic hypoxia. Yackton had no antiradical properties in vitro. We concluded that yackton promotes optimization of prooxidant-antioxidant homeostasis of the organism under the hemic and hypoxic hypoxia acting as antioxidant of a non-direct action.

Animals↗
PubMed2004

Induction of homochirality in achiral enantiomorphous monolayers.

We report the induction of homochirality in enantiomorphous layers of achiral succinic acid on a Cu(110) surface after doping with tartaric acid (TA) enantiomers. Succinic acid becomes chiral upon adsorption due to symmetry-breaking interactions with the Cu(110) surface. The doubly deprotonated bisuccinate forms mirror domains on the surface, which leads to a superposition of (11,-90) and (90,-11) patterns observed by low-energy electron diffraction (LEED). On average, however, the surface layer is racemic. An amount of 2 mol % of (R,R)- or (S,S)-tartaric acid in the monolayer, corresponding to an absolute coverage of 0.001 tartaric acid molecule per surface copper atom, is sufficient to make the LEED spots of one enantiomorphous lattice disappear. After thermally induced desorption of TA, the succinic acid lattice turns racemic again. In analogy to the "sergeants-and-soldiers" principle described for helical polymers, this effect is explained by a lateral cooperative interaction within the two-dimensional lattice.

Cinchona Alkaloids↗