Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Succinates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed1981

Compatibility of mephentermine sulfate with hydrocortisone sodium succinate or aminophylline in 5% dextrose injection.

The compatibility and stability of mephentermine sulfate with hydrocortisone sodium succinate or aminophylline in 5% dextrose injection were studied. Mephentermine sulfate injection (equivalent to mephentermine 300 mg) was added to both hydrocortisone sodium succinate injection (equivalent to hydrocortisone 100 mg--admixture I) and aminophylline injection 250 mg (admixture II), each in 5% dextrose injection 400 ml. The solutions were stored in sealed USP type I containers and stored at 0-4 degrees C, 30 +/- 2 degrees C, and 45 +/- 1 degree C. Aliquots were drawn initially and at 4 and 24 hours for pH, drug content, and degradation product determinations. Mephentermine sulfate content was analyzed by a spectrophotometric method involving ion-pair extraction with tropaeolin 00. Hydrocortisone sodium succinate and aminophylline were analyzed by color reaction with isoniazid and UV spectrophotometry, respectively. The content of mephentermine and total hydrocortisone showed no change in admixture I under all test conditions. Hydrocortisone sodium succinate ester hydrolyzed slowly, but not more than 5% after 24 hours at 45 degrees C. There was no appreciable loss of mephentermine sulfate or aminophylline potency in admixture II. The pH of the solutions did not change over the period of study. The results indicate that both admixtures were compatible and stable under the tested storage conditions for at least 24 hours.

Aminophylline↗
PubMed1996

Seventy-two hour comparison of methylprednisolone suleptanate and methylprednisolone sodium succinate in patients with acute asthma.

The efficacy and safety of the methylprednisolone prodrugs methylprednisolone suleptanate and methylprednisolone sodium succinate were evaluated in a multicentre, randomised, double-blind, double-dummy parallel study of 88 patients hospitalised with acute asthma. Each study drug was administered as a bolus intravenous injection of 40mg methylprednisolone equivalents every 6 hours for 48 hours. Methylprednisolone 32mg was administered orally 6 hours after the last dose. Pulmonary function, medical events, and clinical laboratory values were assessed at predefined intervals before and during the 72-hour study. The primary response measure of pulmonary function was per cent predicted forced expiratory volume in one second (FEV1) at 48 hours. Secondary response measures were peak expiratory flow rate (PEFR) and FEV1/forced vital capacity (FVC) ratio. Although both drugs demonstrated within-group mean changes from baseline (starting at 6 hours) that were statistically significant for each response, there were no statistically significant differences between the two groups. The mean percent predicted FEV1 at 48 hours and mean per cent change from baseline were 64% and 13% (p < 0.0001) for the methylprednisolone suleptanate group and 67% and 17% (p < 0.0001) for the methylprednisolone sodium succinate group, respectively. The mean PEFR and FEV1/FVC ratio at 48 hours were 5.77 l/s and 73% for the methylprednisolone suleptanate group and 5.78 l/s and 76% for the methylprednisolone sodium succinate group, respectively. There were no clinically or statistically significant between-group differences in any of the safety parameters. In this study, methylprednisolone suleptanate and methylprednisolone sodium succinate have been shown to be therapeutically equivalent in the treatment of patients hospitalized with acute asthma.

Acute Disease↗
PubMedDate not supplied

Insulinotropic action of novel succinic acid esters.

The insulinotropic action of several new esters of succinic acid was assessed in isolated rat islets incubated in the presence of 7 mM D-glucose. An efficient secretory response was observed with the monobenzyl, monoisopropyl, monoallyl, monopropyl, monoethyl, monobutyl, dibutyl, dipropyl and diallyl esters of succinic acid. This indicates that it is possible to design esters of succinic acid which act as insulin secretagogues, while avoiding the undesirable generation of methanol that otherwise results from the use of either the monomethyl or dimethyl ester of this dicarboxylic acid.

Animals↗
PubMed1994

Succinate-ethanol fermentation in Clostridium kluyveri: purification and characterisation of 4-hydroxybutyryl-CoA dehydratase/vinylacetyl-CoA delta 3-delta 2-isomerase.

Anaerobically prepared cell extracts of Clostridium kluyveri grown on succinate plus ethanol contained high amounts of 4-hydroxybutyryl-CoA dehydratase, which catalyzes the reversible dehydration of 4-hydroxybutyryl-CoA to crotonyl-CoA. The enzyme was purified 12-fold under strictly anaerobic conditions to over 95% homogeneity and had a specific activity of 123 nkat mg-1. The finding of this dehydratase means that all of the enzymes necessary for fermentation of succinate plus ethanol by C. kluyveri have now been demonstrated to exist in this organism and confirms the proposed pathway involving a reduction of succinate via 4-hydroxybutyrate to butyrate. Interestingly, the enzyme is almost identical to the previously isolated 4-hydroxybutyryl-CoA dehydratase from Clostridium aminobutyricum. The dehydratase was revealed as being a homotetramer (m = 59 kDa/subunit), containing 2 +/- 0.2 mol FAD, 13.6 +/- 0.8 mol Fe and 10.8 +/- 1.2 mol inorganic sulfur. The enzyme was irreversibly inactivated after exposure to air. Reduction by sodium dithionite also yielded an inactive enzyme which could be reactivated, however, up to 84% by oxidation with potassium hexacyanoferrate(III). The enzyme possesses an intrinsic vinylacetyl-CoA isomerase activity which was also found in 4-hydroxybutyryl-CoA dehydratase from C. aminobutyricum. Moreover, the N-terminal sequences of the dehydratases from both organisms were found to be 63% identical.

Amino Acid Sequence↗
PubMed1991

Study of the interaction of cadmium with membrane-bound succinate dehydrogenase.

Cadmium ions inhibit membrane-bound succinate dehydrogenase with a second-order rate constant of 10.42 mM-1 s-1 at pH 7.35 and 25 degrees C. Succinate and malonate protect the enzyme against cadmium ion inhibition. The protection pattern exerted by succinate and malonate suggests that the group modified by cadmium is located at the active site. The pH curve of inactivation by Cd2+ indicates the involvement of an amino acid residue with pKa of 7.23.

Animals↗
PubMed1984

Mitochondrial-microsomal interactions in vitro: use of microsomal 7-ethoxycoumarin O-deethylase to study succinate-stimulated malate efflux from mitochondria.

An assay system was developed utilizing microsomal 7-ethoxycoumarin O-deethylase to monitor the formation and efflux of malate from mitochondria in vitro. Malate was coupled by means of malic enzyme, NADP+, and the microsomal mixed-function oxidase system to the production of highly fluorescent 7-hydroxycoumarin. Under conditions of the assay, steady-state concentrations of NADPH could be maintained, and half-maximal rates of microsomal 7-ethoxycoumarin O-deethylase were observed with about 0.2 microM NADPH and 250 microM malate. Addition of succinate to mixtures of intact mitochondria and microsomes enhanced rates of 7-hydroxycoumarin formation by facilitating the generation and transport of malate from mitochondria (half-maximal stimulation was observed with 0.4 mM succinate). Stimulation of 7-hydroxycoumarin formation by succinate, under conditions where concentrations of cofactors and substrate were adjusted to resemble those in the intact cell, provides further evidence that reducing equivalents for mixed-function oxidation may arise via malate efflux from mitochondria.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1975

EPR studies on the respiratory chain of wild-type Saccharomyces cerevisiae and mutants with a deficiency in succinate dehydrogenase.

1. Three nuclear mutants of Saccharomyces cerevisiae deficient in succinate dehydrogenase have been isolated. Two of these mutants are allelic. 2. The amount of covalently bound flavin of submitochondrial particles of the two allelic mutants is about 14% and that of the third mutant about 50% of the amount in wild-type particles. The turnover number of succinate dehydrogenase of particles is decreased in all mutants. The turnover number of fumarate reductase is increased in the two allelic mutants, but decreased in the third mutant. 3. EPR spectra, measured at 82 degrees K, show that the amplitude of the g equals 1.93 signal in particles of the two allelic mutants is less than 10% of that in wild-type particles. It is concluded that iron-sulphur centres other than those of succinate dehydrogenase make only a negligible contribution to the line at g equals 1.93 in wild-type particles. 4. EPR measurements below 20 degrees K show that the amplitude of the signal at g equals 2.01 detected in oxidized particles is decreased in particles of the two allelic mutants. 5. A signal with lines at g equals 2.027 and g equals 1.933 is detected at low temperatures in all particle preparations, even in those from a cytoplasmic petite mutant. It is suggested that this signal is derived from a contaminant and not from the inner membrane.

Cytochromes↗
PubMed1982

Mitochondrial lipid peroxidation by cumene hydroperoxide and its prevention by succinate.

Rat liver mitochondria form lipid hydroperoxides when they are incubated aerobically with cumene hydroperoxide. The rate of reaction is dependent on the initial concentration of the latter and involves the consumption of oxygen. Gradient-separated and cytochrome c-depleted mitochondria, mitoplasts and submitochondrial fractions also undergo this peroxidation. Mitochondrial lipid peroxidation by cumene hydroperoxide is strongly inhibited by SKF52A (an inhibitor of cytochrome P-450), by antioxidants and to a lesser extent by the enzymes superoxide dismutase and catalase. Conversely, rotenone and N-ethylmaleimide stimulate the reaction. Succinate protects against the lipid peroxidation and in some mitochondrial fractions the associated oxygen uptake is also inhibited. This protection by succinate is prevented by malonate but not by N-ethylmaleimide or antimycin. Lipid hydroperoxides present in previously peroxidised mitochondria are partly lost on reincubation with succinate and this reaction is also unaffected by N-ethylmaleimide but inhibited by both malonate and antimycin. The results suggest that reduction of mitochondrial ubiquinone may prevent the generation of lipid hydroperoxides but that their subsequent removal may require reduction at or beyond cytochrome b.

Animals↗
PubMed1980

The prosthetic groups in succinate dehydrogenase. Number and stoichiometry.

I. Succinate:Q oxidoreductase (EC 1.3.99.1) as present in beef-heart submitochondrial particles contains equal amounts of FAD, a [2Fe-2S] cluster and a [4Fe-4S] cluster. Both Fe-S clusters are reducible by succinate. 2. A second type of [2Fe-2S] cluster, called center S-2, that has been proposed to be present in purified preparations of succinate dehydrogenase and isolated Complex II (Ohnishi, T., Winter, D.B., Lim, J. and King, T.E. (1973) Biochem. Biophys. Res. Commun. 53, 231--237) is an artifact introduced by the purification procedure. 3. It is suggested that the 70 000 dalton subunit which is known to bind the flavin, accomodates also the [4Fe-4S] cluster whereas the 28 000 dalton subunit contains the [2Fe-2S] cluster.

Animals↗
PubMed1988

Succinic acidemia: a new syndrome of organic acidemia associated with congenital lactic acidosis and decreased NADH-cytochrome c reductase activity.

Two siblings with succinic acidemia, a hitherto unreported organic acidemia, were investigated. Succinic acidemia, lactic acidosis and respiratory distress were observed in one of the siblings, who died 37 days after birth, and succinic acidemia was also detected in the next sibling at the fetal stage. NADH-cytochrome c reductase activity was significantly low in both cases and NADH-ferricyanide reductase activity was also low in the fetal case, suggesting a complex I deficiency of the electron transport system in the mitochondrial membrane.

Acidosis, Lactic↗
PubMed1984

Relationships between the effects of redox potential, alpha-thenoyltrifluoroacetone and malonate on O(2) and H2O2 generation by submitochondrial particles in the presence of succinate and antimycin.

The rate of the antimycin-induced H2O2 and O(2) generation in beef heart submitochondrial particles is maximal at the [succinate]/[fumarate] ratio of approximately 1:5 and decays at both higher and lower redox potentials. Succinate dehydrogenase inhibitors, such as TTFA or malonate, stimulate active oxygen production in the presence of excess succinate but are inhibitory at Eh values more positive than the optimal. The modulation of O(2) and H2O2 generation by these inhibitors can be explained by their effects on the steady-state redox potential(s) of the component(s) of mitochondrial site 2.

Animals↗
PubMed1991

A comparative study of succinate-supported respiration and ATP/ADP translocation in liver mitochondria from adult and old rats.

This study was undertaken to compare the rates of succinate-supported hepatic mitochondrial respiration between 12 months (adult) and 29 months (old) male Fischer 344 rats. Experiments were also performed to determine the activity of adenine nucleotide translocase and the effect of its inhibition on mitochondrial respiration. Succinate-supported state 3 mitochondrial respiration was found to decline 20% between 12 and 29 months of age in rat liver, along with a similar 25% decrease in the respiratory control ratio with age. Adenine nucleotide translocase activity is shown to decrease 39% from adult to old rat liver mitochondria. This decrease does not, however, account for the decline in state 3 respiration, since translocase activity is approximately 50% greater than state 3 respiration in both adult and old rats. Therefore, adenine nucleotide translocase is not rate-limiting for state 3 mitochondrial respiration. Neither the rate of succinate permeation into the mitochondrial nor the rate of electron transport is rate-limiting for state 3 respiration, indicated by the greatly increased oxygen consumption with addition of the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (m-CCCP). These processes, therefore, are not responsible for the observed decline in state 3 respiration. The implications and possible cause of the age-related decrease in the maximal rate of ATP-synthesis are discussed.

Adenosine Diphosphate↗
PubMed1981

Succinate decarboxylation to propionate and the associated phosphorylation in Fasciola hepatica and Spirometra mansonoides.

The trematode, Fasciola hepatica, and the cestode, Spirometra mansonoides have been shown to be similar to the nematode Ascaris lumbricoides in that all three decarboxylate succinate to propionate plus CO2. Associated with this decarboxylation is an incorporation of 32Pi into organic phosphate. Both the decarboxylation and phosphorylation are markedly stimulated by the addition of propionyl-CoA, are dependent on coenzyme B12 and are inhibited by avidin. The trematode and cestode exhibit propionyl-CoA carboxylase, methylmalonyl-CoA mutase and acyl-CoA transferase activities in sonicated mitochondrial preparations. Data are consistent with the occurrence of a mitochondrial substrate level site for ATP generation which is coupled with the decarboxylation of succinate. In Fasciola preparations, acetyl-CoA stimulates the decarboxylation and phosphorylation to a considerably larger extent than propionyl-CoA, indicating the possibility that acetyl-CoA may serve physiologically in these reactions by donating the CoA moiety to succinate.

Acetyl Coenzyme A↗
PubMed1994

Release of alpha-ketoglutarate, malate and succinate from cultured astrocytes: possible role in amino acid neurotransmitter homeostasis.

The rates of release of the tricarboxylic acid (TCA) cycle constituents alpha-ketoglutarate (alpha-KG), malate and succinate were determined in cultured mouse cerebellar astrocytes, cerebellar granule neurons and cerebral cortical neurons. In addition, its dependence on the external HCO3- concentration was investigated together with effects of K+, glutamate and glutamine. The rate of release of these TCA cycle constituents was linear with time for at least 48 h regardless of the cell type. The release was for all 3 compounds much higher in the astrocytes (13.1, 3.8 and 1.5 nmol.h-1.mg-1 for alpha-KG, malate and succinate, respectively) than in cerebellar (6.5 and 1.5 for alpha-KG and malate) and cortical (3.5 and 1.2 for alpha-KG and malate) neurons. Release of succinate in the neurons could not be determined accurately due to the sensitivity of the assay. In the astrocytes the release of alpha-KG and malate was dependent on HCO3- in a saturable manner with Km values around 6 and 1 mM for alpha-KG and malate, respectively. The release of alpha-KG and malate from astrocytes was stimulated by glutamate (0.5 mM) whereas K+ (15 and 55 mM) and glutamine (0.5 mM) had no effect. The results clearly demonstrate that astrocytes but not neurons release appreciable amounts of TCA cycle intermediates reflecting the presence of pyruvate carboxylase in these cells. The exact functional importance of this release remains to be established but it could play some albeit a minor quantitative role for neuronal homeostasis of the neurotransmitter amino acids glutamate and GABA.

Animals↗
PubMed1993

Succinate-cytochrome c reductase: assessment of its value in the investigation of defects of the respiratory chain.

Defects of the respiratory chain are important causes of human disease and one of the most commonly used assays in the investigation of these patients is the measurement of succinate-cytochrome c reductase. However, this assay measures several components of the respiratory chain and the ability to detect a partial defect in one enzyme complex will depend on the amount of control exerted by that enzyme step on overall electron flux. We show that measurement of succinate-cytochrome c reductase activity may fail to detect partial defects of complex III and therefore is of limited diagnostic value in the identification of complex III defects. However, complex II is a major point of control of flux through succinate-cytochrome reductase and it is likely that measurement of the latter will detect defects of complex II.

Animals↗
PubMed2006

Redox stress is not essential for the pseudo-hypoxic phenotype of succinate dehydrogenase deficient cells.

HIFalpha prolyl hydroxylases (PHDs) are a family of enzymes that regulate protein levels of the alpha subunit of the hypoxia inducible transcription factor (HIF) under different oxygen levels. PHDs catalyse the conversion of a prolyl residue, molecular oxygen and alpha-ketoglutarate to hydroxy-prolyl, carbon dioxide and succinate in a reaction dependent on ferrous iron and ascorbate as cofactors. Recently it was shown that pseudo-hypoxia, HIF induction under normoxic conditions, is an important feature of tumours generated as a consequence of inactivation of the mitochondrial tumour suppressor 'succinate dehydrogenase' (SDH). Two models have been proposed to describe the link between SDH inhibition and HIF activation. Both models suggest that a mitochondrial-generated signal leads to the inhibition of PHDs in the cytosol, however, the models differ in the nature of the proposed messenger. The first model postulates that mitochondrial-generated hydrogen peroxide mediates signal transduction while the second model implicates succinate as the molecular messenger which leaves the mitochondrion and inhibits PHDs in the cytosol. Here we show that pseudo-hypoxia can be observed in SDH-suppressed cells in the absence of oxidative stress and in the presence of effective antioxidant treatment.

Antioxidants↗
PubMed2002

Succinate:quinone oxidoreductases from epsilon-proteobacteria.

The epsilon-proteobacteria form a subdivision of the Proteobacteria including the genera Wolinella, Campylobacter, Helicobacter, Sulfurospirillum, Arcobacter and Dehalospirillum. The majority of these bacteria are oxidase-positive microaerophiles indicating an electron transport chain with molecular oxygen as terminal electron acceptor. However, numerous members of the epsilon-proteobacteria also grow in the absence of oxygen. The common presence of menaquinone and fumarate reduction activity suggests anaerobic fumarate respiration which was demonstrated for the rumen bacterium Wolinella succinogenes as well as for Sulfurospirillum deleyianum, Campylobacter fetus, Campylobacter rectus and Dehalospirillum multivorans. To date, complete genome sequences of Helicobacter pylori and Campylobacter jejuni are available. These bacteria and W. succinogenes contain the genes frdC, A and B encoding highly similar heterotrimeric enzyme complexes belonging to the family of succinate:quinone oxidoreductases. The crystal structure of the W. succinogenes quinol:fumarate reductase complex (FrdCAB) was solved recently, thus providing a model of succinate:quinone oxidoreductases from epsilon-proteobacteria. Succinate:quinone oxidoreductases are being discussed as possible therapeutic targets in the treatment of several pathogenic epsilon-proteobacteria.

Citric Acid Cycle↗
PubMed2002

Reactive oxygen species inhibit the succinate oxidation-supported generation of membrane potential in wheat mitochondria.

In order to gain a first insight into the effects of reactive oxygen species (ROS) on plant mitochondria, we studied the effect of the ROS producing system consisting of xanthine plus xanthine oxidase on the rate of membrane potential (DeltaPsi) generation due to either succinate or NADH addition to durum wheat mitochondria as monitored by safranin fluorescence. We show that the early ROS production inhibits the succinate-dependent, but not the NADH-dependent, DeltaPsi generation and oxygen uptake. This inhibition appears to depend on the impairment of mitochondrial permeability to succinate. It does not involve mitochondrial thiol groups sensitive to either mersalyl or N-ethylmaleimide and might involve both protein residues and/or membrane lipids, as suggested by the mixed nature. We propose that, during oxidative stress, early generation of ROS can affect plant mitochondria by impairing metabolite transport, thus preventing further substrate oxidation, DeltaPsi generation and consequent large-scale ROS production.

Kinetics↗