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PubMed1984

Effects of succinate on amino acid incorporation into protein during chemical carcinogenesis.

The starting point of this study is the observation that succinate, the well-known Krebs cycle intermediate, strongly inhibits the incorporation of amino acids into protein of tissue slices. The results presented in this paper show that this somewhat peculiar succinate effect, which is present in regenerating liver and in a well-differentiated hepatoma and absent in two anaplastic hepatomas, is well-marked in all stages of hepatic carcinogenesis by N,N'-dimethyl-4-aminoazobenzene. A working hypothesis is that the inhibition by succinate of the amino acid incorporation into protein is mediated by a shift of the redox level in the cell toward a more reduced condition.

Amino Acids↗
PubMed1980

Propionate inhibition of succinate:CoA ligase (GDP) and the citric acid cycle in mitochondria.

Propionate inhibits oxygen consumption by rat liver mitochondria when glutamate, alpha-ketaglutarate, and succinate are substrates. Carnitine prevents this effect. The pattern of inhibition of 14CO2 release from metabolic intermediates indicates citric acid cycle inhibition between succinate:coenzyme A (CoA) ligase (GDP) and malate dehydrogenase. Propionyl CoA is synthesized from propionate in mitochondria. Propionyl CoA is a potent inhibitor of succinate:CoA ligase with positive cooperativity and half half-maximal inhibition at 2 X 10(-4) M propionyl CoA.

Acyl Coenzyme A↗
PubMed1988

Citric, malic and succinic acids as possible alternatives to deferoxamine in aluminum toxicity.

The effect of repeated intraperitoneal administration of deferoxamine, citric, malic and succinic acids on the distribution and excretion of aluminum was determined in male Swiss mice which had previously received aluminum nitrate intraperitoneally at a daily dose of 0.27 mmol/kg for five weeks. Chelating agents were administered for two weeks at doses approximately equal to one-fourth of their respective LD50. Treatment with DFOA, citric, malic or succinic acids significantly increased the fecal and urinary excretion of aluminum and reduced the concentration of aluminum found in various organs and tissues, with citric acid being the most effective. In sight of these results, citric, malic or succinic acids may be considered as alternatives to deferoxamine in aluminum toxicity. However, further investigations are required previous to the possible use of these compounds in human aluminum poisoning.

Aluminum↗
PubMed1990

Enzymes of PEP-succinate pathway in Setaria cervi and effect of anthelmintic drugs.

Localization of different enzymes of PEP-succinate pathway has been done in Setaria cervi, a bovine filarial worm. Succinate dehydrogenase and fumarate reductase were localized in mitochondria rich particulate fraction while all other enzymes were cytosolic. The in vitro effect of certain antifilarial/anthelmintic agents on these enzymes was also investigated. Sumarmin, at low concentration, could cause a marked inhibition of most of the enzymes of this pathway. Centperazine, an antifilarial drug being developed by CDRI showed significant inhibitory action on pyruvate kinase, lactate dehydrogenase, fumarase and succinate dehydrogenase while CDRI compound 72/70 showed significant inhibition of PEP-carboxykinase activity. Diethylcarbamazine and levamisole, however, were found to be more or less ineffective at lower concentrations against all the enzymes of this pathway.

Animals↗
PubMed1989

[Determining the conditions for stimulation of levorin biosynthesis in the presence of succinic acid].

Conditions promoting the stimulating effect of succinic acid on biosynthesis of levorin were determined. The optimal concentration of succinate was shown to be equal to 0.05-0.3 per cent and the best time for the addition was before inoculation. The most pronounced stimulating effect was observed when the initial pH value of the fermentation medium was equal to 7.0. The important role of ammonium nitrogen in manifestation of the succinic acid stimulating effect on biosynthesis of levorin was suggested.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Effect of succinic acid on blood coagulability and the catecholamine balance].

A single administration of succinic acid was shown to cause a dose-dependent decrease of the blood coagulability in rats. Seven-day administration of succinic acid (50 mg/kg) resulted in a distinct increase of the blood coagulability, an accumulation of adrenaline in the heart and adrenal gland tissues. Hypercoagulation was noted on the 5th day after withdrawal of succinic acid (50 and 200 mg/kg).

Adrenal Glands↗
PubMed1984

[Effect of sodium succinate on metabolic and morphological changes in acute cooling].

The effect of sodium succinate preinjection (16 mg/kg) on the resistance of mice to acute low-temperature exposure was studied. The measurements were taken of the changes in blood glucose concentration, of the content in the heart of macroergic compounds and glycogen, and of succinate dehydrogenase activity. Cardiomyocytes were studied by electron microscopy. The data indicate that greater preservation of macroergic compounds and stabilization of the ultrastructure of myocardial mitochondria play a role in the mechanism by which the animals' resistance to intense cooling is increased after sodium succinate injection.

Acute Disease↗
PubMed1983

Excess rumen product anions in cattle. I. Blood clearance rates and reduced liver function from sublethal doses of volatile fatty acids, lactate and succinate.

Blood clearance rates of volatile fatty acids, lactate and succinate were estimated in cattle following a single rapid intravenous injection of a Na-anion solution. Bromosulfophthalein was administered immediately before the anion to monitor the effects upon liver function, blood circulation, and dose equilibrium. Acetate, propionate, and valerate at doses up to 5 mmole/kg were cleared quickly from the blood by a first-order process without effects either upon the animal or bromosulfophthalein clearance. Injection of acetic acid solutions produced no effects. Butyrate was toxic at doses above 1 mmole/kg and progressively affected both the rate and progress of bromosulfophthalein clearance as the dose increased. Lactate and succinate were toxic and lethal at doses around 0.25 mmole/kg, and caused both reduced rates and altered progress of bromosulfophthalein clearance. The toxic reactions resulted in total collapse from loss of muscle tone. The butyrate and lactate effects were accentuated when the anion solutions were injected at low pH where a large portion of the anion would be unionized. Levels of butyrate, lactate and succinate in the rumens of feedlot cattle were high enough to provide toxic doses of these anions. The results are discussed in terms of the effects of excess rumen production of these anions upon the liver function and health of feedlot cattle.

Animals↗
PubMed1982

Stoichiometry of Na+-succinate cotransport in renal brush-border membranes.

The coupled transport of Na+ with succinate and citrate into rabbit renal brush-border membrane vesicles was studied. Initial rates of transport (J) were estimated from 1-s uptakes under well defined transmembrane conditions (membrane potential, pH, ionic composition). A Na+ gradient increased J up to 700 times compared to Na+ replacement with sorbitol. J was a sigmoid function of increasing Na+ concentration; the kinetic interaction of Na+ with the succinate-citrate transport system was described by the equation: J = Jmax/(1 + (Ks/[Na]))3. Assuming that the Na+ interaction involves equivalent, noninteracting binding sites, these results indicate that 3 Na+ ions are translocated/molecule of organic substrate. Consistent with the latter observation was the direct demonstration of a stoichiometric coupling between simultaneously determined fluxes of 22Na+ and 14C-labeled substrates. In excess of 2 Na+ ions were transported/molecule of organic substrate. These results explain the electrogenicity of the transport of succinate and citrate as evidenced by the response of J to K+ diffusion potentials and the effects of transport on the fluorescence of a potential-sensitive cyanine dye.

Animals↗
PubMedDate not supplied

[Effect of tubaside and sodium succinate on oxidative phosphorylation and p-hydroxylation in the liver].

Tubaside causes disturbances in oxidative phosphorylation of the liver mitochondria. Sodium succinate administered during tubaside intoxication favours normalization of the oxygen uptake rate in state 3 and the ADP phosphorylation rate. Sodium succinate weakens the toxic effect of tubaside and favours normalization of p-hydroxylation in the liver. The animals, which were given tubaside in combination with sodium succinate are characterized by a higher survival rate.

Animals↗
PubMedDate not supplied

[Effects of sodium succinate on functional, biochemical and morphological indicators of CNS repair in rats after 10-minute circulation arrest].

Therapeutic effect of sodium succinate on various functional, biochemical, and morphological parameters of CNS repair was studied in experiments on rats exposed to 10-min circulation arrest. The first series of experiments was devoted to studies of the effects of the drug, injected intraperitoneally directly after recovery of effective cardiac activity and during the subsequent 5 days in doses 20, 100, and 200 mg/kg, on the survival and recovery of the external neurologic status. The dose of 20 mg/kg proved to be the most effective. The second series of experiments was devoted to therapeutic effect of sodium succinate in the same dose injected from day 3 to day 7 after revival on the orientation and investigation behaviour in an "open field" test, on changes in radical formation in the blood serum and the brain, and on the cholesterol/lipid ratio in the brain, as well as on the morphologic changes in the cerebral hemispheres and the cerebellum. In contrast to untreated animals, the treated ones had a less intensive reaction in the "open field" test in response to acute stressor exposure, their cerebral and blood serum levels of free radical processes were reduced, the destruction of neuronal membranous elements was less intensive, as were dystrophic changes in the cerebral cortex and the cerebellum. The data permit a conclusion about antistressor and protective effect of sodium succinate in the postresuscitation period at the functional, biochemical, and morphological levels.

Animals↗
PubMedDate not supplied

Stimulation of insulin release caused by intraduodenal administration of succinic acid methyl esters.

The methyl esters of succinic and glutamic acid are currently under investigation as possible tools for stimulation of insulin biosynthesis and release in non-insulin-dependent diabetes mellitus. The present study deals with the secretory response of the pancreatic B-cell to these esters after intraduodenal administration to anaesthetized rats. The dimethyl ester of succinic acid and, to a lesser extent, its monomethyl ester both increased the plasma insulin concentration, whilst the dimethyl ester of glutamic acid virtuality failed to do so. The stimulation of insulin release, caused by the dimethyl ester of succinic acid, was faster and more pronounced than that evoked by an equimolar amount of glucose. The present study thus reveals that the latter ester, when administered via the gastrointestinal tract, evokes a more brisk and more ample secretory response of the pancreatic B-cell than that evoked by glucose.

Animals↗
PubMed1976

Anorectal pruritus after intravenous hydrocortisone sodium succinate and sodium phosphate.

A double-blind study demonstrated that single intravenous doses of 100, 200, or 400 mg of hydrocortisone sodium succinate and hydrocortisone sodium phosphate were similar in eosinophil suppression, elevation of glucose, white blood count differential shifts (polymorphonuclear cells, lymphocytes, and monocytes), and urinary excretion of sodium and potassium but not in incidence of side effects. More subjects receiving hydrocortisone sodium phosphate experienced systemic or localized adverse effects than those receiving hydrocortisone sodium succinate. The most common side effect was burning or itching in the anorectal area, which occurred in 16 of 18 subjects medicated with hydrocortisone sodium phosphate, in 1 subject of 6 treated with placebo (saline), and in none who received the sodium succinate. The effect is attributed to the phosphate steroid and appears to last as long as it takes to convert to cortisol.

Adult↗
PubMed1990

A 13C NMR study of the application of [U-13C]succinate for metabolic investigations in rabbit renal proximal convoluted tubular cells.

The fate of the 13C label arising from [U-13C]succinate in rabbit renal proximal convoluted tubular (PCT) cells, incubated with [U-13C]succinate, was investigated by 13C NMR spectroscopy of the perchloric acid extracts of the cell pellets. The 13C label of [U-13C]succinate was predominantly metabolized into glutamate, glutamine, and into glucose, lactate, and alanine, which is the consequence of a carbon efflux of the label from the Krebs cycle at the stage of alpha-ketoglutarate and oxaloacetate, respectively.

Animals↗
PubMed2001

Acidianus ambivalens Complex II typifies a novel family of succinate dehydrogenases.

Complex II from the thermoacidophilic archaeon Acidianus ambivalens, an archetype of an emerging class of succinate dehydrogenases (SDH), was extracted from intact membranes and purified to homogeneity. The complex contains one molecule of covalently bound FAD and 10 Fe atoms. EPR studies showed that the complex contains the canonical centres S1 ([2Fe-2S]2+/1+) and S2 ([4Fe-4S]+2/+1) but lacks centre S3 ([3Fe-4S]+1/0); these observations agree with the fact that the iron-sulfur subunit contains an extra cysteine that may allow the binding of a new centre, most probably a tetranuclear one. Succinate-driven oxygen consumption is observed in intact membranes indicating that in vivo, complex II operates as a succinate:quinone oxidoreductase, despite missing the typical anchor domain subunits. The pure complex was found to contain bound caldariella quinone, the enzyme physiological partner. An alternative membrane anchoring for this new type of SDHs, based on the amphipathic nature of the putative helices found in SdhC, is suggested.

Amino Acid Sequence↗
PubMed2000

New esters of succinic acid and mixed molecules formed by such esters and a meglitinide analog: study of their insulinotropic potential.

Eighteen novel esters of succinic acid, including three mixed molecules formed of both succinic acid and nateglinide, were examined for their insulinotropic efficiency in isolated rat pancreatic islets. The secretory response to these esters at increasing concentrations of both d -glucose and the ester itself allowed to identify five esters judged of potential interest for further investigations. They include three molecules with CH(3)-O-CO-CH(2)-CH(2)-CO-NH-CH(R)-CO-O- sequence and two mixed molecules with a nateglinide moiety. The effects of the most potent molecule in the first group and that of two of the esters with a nateglinide moiety upon islet biosynthetic activity in vitro and insulin release in vivo, after either oral or intravenous administration were also investigated. The results suggested that mixed molecules formed of both a succinic acid ester and a meglitinide analog may efficiently stimulate proinsulin biosynthesis and/or insulin release. Further work is required, however, to improve their modality of in vivo administration.

Animals↗
PubMed1986

Pleiotropic mutations in appR reduce pH 2.5 acid phosphatase expression and restore succinate utilisation in CRP-deficient strains of Escherichia coli.

Several strains of Escherichia coli K12 were compared for activity of the periplasmic "pH 2.5 acid phosphatase", an enzyme whose expression is regulated negatively by cyclic AMP. Two distinct enzyme levels differing by about four-fold were observed. This strain-dependent difference does not involve modifications in the structure of the enzyme, but results from a difference in its expression. We show that strains with a high- or a low level of enzyme differ in the gene locus appR located in the 59 min region of the chromosome, a site remote from the structural gene appA; the appR+ versus appR enzyme ratio is 3-4 in wild-type strains, adenylate cyclase-deficient strains (cya) or cyclic AMP receptor protein-deficient strains (crp) grown in rich medium or in glucose minimal medium, but is close to 1 in cya strains in the presence of 0.1 mM cyclic AMP and in wild-type strains grown with succinate as carbon source; in a crp genetic background, appR strains, contrary to appR+ strains, are able to grow on minimal medium with succinate as the sole carbon source. The selection, from an appR+ crp strain, of clones growing on succinate-minimal medium, yielded mutations in the same region of the chromosome and showing the same phenotype as "naturally-occurring" appR strains. All appR strains analysed so far showed other similar deficiencies. The possibility that mutated appR gene products might function as weak substitutes for a functional cAMP-CRP complex is discussed.

Acid Phosphatase↗
PubMed1978

The pathway of formation of acetate and succinate from pyruvate by Bacteroides succinogenes.

Bacteroides succinogenes produces acetate and succinate as major products of carbohydrate fermentation. An investigation of the enzymes involved indicated that pyruvate is oxidized by a flavin-dependent pyruvate cleavage enzyme to acetyl-CoA and CO2. Active CO2 exchange is associated with the pyruvate oxidation system. Reduction of flavin nucleotides is CoASH-dependent and does not require ferredoxin. Acetyl-CoA is further metabolized via acetyl phosphate to acetate and ATP. Reduced flavin nucleotide is used to reduce fumarate to succinate by a particulate flavin-specific fumarate reductase reaction which may involve cytochrome b. Phosphoenolpyruvate (PEP) is carboxylated to oxalacetate by a GDP- specific PEP carboxykinase. Oxalacetate, in turn, is converted to malate by a pyridine nucleotide-dependent malate dehydrogenase. The organism has a NAD-dependent glyceraldehyde-3-phosphate dehydrogenase. The data suggest that reduced pyridine nucleotides generated during glycolysis are oxidized in malate formation and that the electrons generated during pyruvate oxidation are used to reduce fumarate to succinate.

Acetates↗