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Properties of human serum low density lipoproteins after modification by succinic anhydride.

Human serum low density lipoprotein of d 1.019-1.063 (LDL(2)) treated with succinic anhydride at pH 7.5-8.0 showed the same chemical composition, hydrodynamic properties (flotation and sedimentation coefficients, intrinsic viscosity) and optical properties (circular dichroism) as untreated LDL(2). However, in contrast to LDL(2), the succinylated product (s-LDL(2)) failed to react with rabbit anti-LDL(2) antisera. Extraction with ethanol-ether 3:1 yielded the succinylated apoprotein (s-apo-LDL(2)), which was, unlike untreated apoprotein, soluble in aqueous buffers. Succinylated apoprotein, which was also immunologically unreactive, appeared to differ in structure from s-LDL(2), as assessed by the parameters of intrinsic viscosity and circular dichroism. The molecular weights of both LDL(2) and s-LDL(2) obtained by the technique of sedimentation equilibrium were 2.1-2.3 x 10(6). By the same method, s-apo-LDL(2) gave an uncorrected figure of 3.95-4.15 x 10(4) and, after correction for succinyl functions, of 3.60-3.80 x 10(4). Because of the assumptions made in the computations, the latter figure was considered approximate. The marked differences in molecular weight between s-apo-LDL(2) and whole apo-LDL(2) ( approximately 5 x 10(5)) were taken to support the subunit structure of apo-LDL(2), which is envisaged as an aggregate of about 12 subunits which dissociate upon succinylation. Further, the large percentage (about 90%) of the free amino groups of LDL(2) found to react with succinic anhydride suggests that these groups are at the surface of the molecule.

Amino Acids↗

[Iron absorption after oral application of a combination of Fe2+-succinate and multivitamins (author's transl)].

The rate of iron absorption of Fe2+-succinate orally applied with multivitamins, was measured by means of whole-body counter in 45 subjects. The dosage was 330 mg ferrous succinate (115 mg Fe2+). Absorption was generally 4.5% (5.2 mg) in normal subjects, 8.6% (9.9 mg) in subjects with latent iron deficiency, and 29.6% (34 mg) in subjects with manifest iron deficiency. In women taking oral contraceptives and not suffering from iron deficiency, no significant increase in the iron absorption rate was measured.

Administration, Oral↗

[Effect of vagotomy on glycogen content, succinate dehydrogenase, cytochrome-c-oxidase and lactate dehydrogenase activities in myocardium in experimental aortostenosis].

The glycogen contents, succinate dehydrogenase, cytochrome-c-oxidase and lactate dehydrogenase activities in tissues of cardiac left cavity of vagotomized and nonvagotomized rabbits were studied two days and two weeks after aortostenosis and false operation. It is established that in vagotimized rabbits the prolongation of the hyperfunction period causes a less pronounced decrease in the glycogen level and a higher level of the succinate dehydrogenase and cytochrome-c-oxidase activities. A conclusion is drawn that heart hyperfunction under conditions of vagotomy is accompanied by a less pronounced inhibition of aerobic and insignificant intensification of anaerobic oxidation processes as compared to their changes in rabbits with the heart maintained innervation.

Anaerobiosis↗

[Role of hydrophobic interactions and functional groups in the inhibitor binding to various sites of mitochondrial succinate-cytochrome c reductase].

It was shown that the efficiency of succinate-cytochrome c reductase inhibitors, i. e. neutral polar substances, negatively charged phenols and 2-hydroxy-3-alkyl-1.4-naphthoquinones, is increased with an increase in their hydrophobicity. Plotting-lg C50 versus lg P for all the three groups of inhibitors, the role of functional groups of the inhibitors in their binding to the corresponding sites of the respiratory chain was determined. The efficiency of inhibition by neutral polar substances does not depend on the chemical nature of the inhibitors and is described by the equation-lg C50 = 0.864 lg P + 0.222 (r = 0.99). The negatively charged group of dissociated phenols determines the specificity of the inhibitor binding to the terminal site of the succinate dehydrogenase complex and is involved in the inhibitor binding to the enzyme. The carbonyl group of 2-hydroxy-3-alkyl-1.4-naphthoquinones selectively increases the affinity and efficiency of binding of these inhibitors to the b-c1 site of the respiratory chain.

Animals↗

Mitochondrial number, cytochrome oxidase and succinic dehydrogenase activity in Xenopus laevis oocytes.

An estimate has been made of the numbers of mitochondria in the mitochondrial cloud (Balbiani body) of Xenopus laevis oocytes ranging in size from 50 to 250 micrometers. The mitochondrial number is expressed in terms of a 'standard' organelle measuring 2 micrometers in length and 0.2 micrometer in diameter and is derived by measurements on electron micrographs of sections through the cloud. It is found that the amount of mitochondrial material rises very rapidly as the oocyte grows in size. At the time the cloud disperses, in oocytes of about 300 micrometers in diameter, it is estimated that there are the equivalent of over 500 000 mitochondria in each cell. The rate of increase is very similar to the rate of accumulation of mitochondrial DNA during the same period of growth. Using a polarographic technique the specific activity of cytochrome oxidase and succinic dehydrogenase was determined in mitochondrial fractions isolated from oocytes over a size range of 80-1200 micrometers in diameter. Although the specific activity of succinic dehydrogenase remains constant that of cytochrome oxidase falls sharply during the period when the mitochondria are replicating rapidly, i.e. up to about 300 micrometer diameter. In larger oocytes the specific activity of enzymes appears to remain constant but increasing contamination of the isolated mitochondrial fraction does not allow conclusions to be drawn from the enzyme loading of the mitochondria once they have dispersed from the cloud. The results are discussed in relation to the possibility that mitochondrial replication preceeds, or at least outpaces, mitochondrial differentiation during the course of oogenesis.

Animals↗

[Succinate dehydrogenase and cytochrome oxidase activity in rat tissues during prolonged hypokinesia].

The activity of cytochrome oxidase in the liver, skeletal muscles, kidneys, brain and lungs of 56 white rats decreased on days 15 and 60 of the hypokinetic study. The activity of succinate dehydrogenase significantly lowered in the brain and slightly diminished in the lungs and skeletal muscles on the same days. The activity of succinate dehydrogenase in the liver increased on the 90th hypokinetic day.

Animals↗

Iron-sulfur cluster 3 of beef heart succinate-ubiquinone oxidoreductase is a 3-iron cluster.

From a study of the magnetic field dependence of the linear electric field effect (LEFE) in EPR spectroscopy, we demonstrate that iron-sulfur cluster 3 in air-oxidized, beef heart succinate-ubiquinone oxidoreductase (Complex II) is a 3-iron cluster. This suggests that cluster 3 may arise by oxidative degradation from a 4-iron cluster originally present in the enzyme and may be reconverted back into a 4-iron cluster under reducing conditions. Linear electric field effect studies of succinate-reduced Complex II are in accord with the view that cluster 1 is a 2-iron cluster.

Animals↗

[Energy-dependent inhibition of mitochondrial NAD.H-oxidase and succinic oxidase by strong nitrous bases].

The inhibitory effect of organic cations from the group of hydrazones on phosphorylated respiration in mitochondria with a succinate as a substrate has been shown to be completely reversed by 2,4-dinitrophenol (DNP). The effect observed has not been due to the action directly on the ATP-synthetase because the inhibition of ATPase, NADH-succinate oxidase and ascorbate oxidase activities occurs at a wide concentration range of compounds studied. The concentration of organic cations used for the inhibition of the respiration in submitochondria particles (SMP) as compared with respiration in mitochondria is higher; in case of SMP the inhibitory effect is not reversed by DNP. These results allow to conclude that the high inhibitory effect of organic cations is due to the energy-dependent binding of these compounds to the enzyme in the membrane phase of mitochondria.

Animals↗

Perinatal development of the distributions of phosphoenolpyruvate carboxykinase and succinate dehydrogenase in rat liver parenchyma.

Parenchymal distributions and activities of mitochondrial succinate dehydrogenase and cytosolic phosphoenolpyruvate carboxy-kinase were studied during perinatal development of rat liver. 1. Succinate dehydrogenase activity increased almost linearly from day 5 before to day 5 after birth. Hepatocytes with higher enzyme activities were disseminated heterogeneously, zonal heterogeneity developed during the second week. 2. Cytosolic phosphoenolpyruvate carboxykinase was not detectable before birth; it was induced to high levels during day 1 and increased further to a maximum during days 5 to 10. It decreased again to adult levels at the end of the third week. The enzyme distribution already showed signs of a zonal heterogeneity at day 1, which became fully developed during the second week. The results indicate that the zonal heterogeneity typical of adult liver was established for the two enzymes during the second week of life. They revealed in addition that the two enzymes, representing two different subcellular compartments, had an individual development towards the zonal heterogeneity.

Age Factors↗

[Effect of sodium fluoride on succinate dehydrogenase and NADH: cytochrome c-reductase of rat liver mitochondria].

It is established that sodium fluoride inhibits the activity of isolated soluble dehydrogenase and succinate dehydrogenase in the rat liver mitochondria in experiments in vitro. The degree of inhibition depends on the fluoride concentration and period of action. At the same time no changes are observed in the NADH-dehydrogenase activity of the mitochondria in the presence of 100 mM of sodium fluoride. With the intragastric administration of 35 and 24 mg/kg sodium fluoride to animals for 3 and 60 days, respectively, the succinate and NADH-dehydrogenase activities of the rat liver mitochondria lower significantly.

Animals↗

Pathology of experimental radiation pancarditis. II. Correlation between ultrastructural changes of the myocardial mitochondria and succinic dehydrogenase activity in rabbit heart receiving a single dose of X-ray irradiation.

Twenty-three rabbits were given a single dose of 3,000R X-irradiation over the heart to study the correlation between the ultrastructural changes of myocardial mitochondria and succinic dehydrogenase activity. The study was made from 1 hour until 1 month after irradiation. The myocardial mitochondria showed, at 1 hour, regressive changes such as irregular arrangement, swelling, vacuolation, decrease and disappearance of cristae, formation of giant mitochondria, and whorled myelin figures. These changes became maximum at 12 hours-2 days. Regeneration of mitochondria had begun at 2 days. At 4-7 days, structurally normal mitochondria had markedly proliferated accompanied by large mitochondria with concentrically arranged cristae and small mitochondria around the nuclei and beneath the sarcolemma of myocardial cells. The myocardial succinic dehydrogenase activity, on the other hand, showed the lowest value at 12 hours--2 days, and recovered almost to the normal value at 7 days. At 2 weeks--1 month when myocardial fibrosis developed, however, the value again mildly decreased. Cardiac death due to radiation therapy may be initiated by the mitochondrial hypofunction in radiation myocardial fibrosis, because the irradiation injures the mitochondrial membrane resulting in morphological and functional changes.

Animals↗

[Therapy of juvenile iron deficiency with bivalent iron dragees (Fe2-fumarate, succinate, sulfate). Controlled double-blind study].

In 53 children with moderate iron deficiency (haemoglobin 7,5 to 12 g/dl) divalent iron salts as tablets (59Fe2+-fumarate, -succinate, -sulfate) were tested versus placebo (controlled double-blind study). Gastrointestinal side effects were most frequently seen with iron succinate (50%) and iron sulfate (25%). Therapeutic success as measured by haemoglobin regeneration was not significantly different among the three iron salts, but significantly more effective than in the placebo group. Children beyond the age of two years mostly refused the application of tablets and should be supplied with liquid preparations.

Anemia, Hypochromic↗

[Lymphocyte succinate dehydrogenase and acid phosphatase activity in infants on artificial feeding with a varying protein content in the diet].

The activity of succinate dehydrogenase and acid phosphatase in blood lymphocytes was studied in healthy children of the first half year of life kept on formula feeding with the adapted milk mixtures "Malyutka" and "Malysh". The content of protein in the children's diet varied over the range of 2-2.5; 3-3.5 and 4-4.5 g/kg. The activity of succinate dehydrogenase has been shown to be related to the protein content in the diet. The results obtained point to the possibility of assessing this activity as an additional method for determination of the optimum protein content in formula feeding.

Acid Phosphatase↗

1-Methyl-4-phenylpyridinium (MPP+) inhibits mitochondrial oxygen consumption mediated by succinate as well as malate in rat pheochromocytoma PC12 cells.

When rat pheochromocytoma PC12 cells are cultured with 1 mM 1-methyl-4-phenylpyridinium (MPP+), the number of viable cells decreases to one third in 4 days while the number increases ten-fold without MPP+. Oxygen consumption by mitochondria in the presence of malate is inhibited about 80% by the treatment of the cells with MPP+ for 4 days. Unexpectedly, succinate-dependent oxygen consumption is also inhibited to essentially the same extent as malate-dependent one. These results suggest that the impairment of the respiration mediated by succinate as well as malate is important as a mechanism of MPP(+)-induced cell death.

1-Methyl-4-phenylpyridinium↗

Concentrations of erythromycin in serum and tonsil: comparison of the estolate and ethyl succinate suspensions.

Concentrations of erythromycin were measured in serum and tonsil from children who had received either the estolate or ethyl succinate suspension before surgery. The in vitro assay measured total erythromycin activity against a group A beta hemolytic streptococcus. Levels of erythromycin in serum and tonsil after single and multiple doses of the estolate were significantly higher than those after administration of the ethyl succinate. The therapeutic implications of these findings are unknown.

Biological Availability↗

Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia.

In rats injected with bacterial lipopolysaccharide (LPS; 5 gamma mg/g body weight [BWT]), the toxin provokes death within 24 h in 23% of the animals and, in surviving rats, causes a decrease in BWT, hyperlactacidemia, hyperlipacidemia, and hyperketonemia, as well as depletion of both liver and muscle glycogen content. In the liver, LPS severely lowers the ATP and total adenine nucleotide content, ATP/ADP ratio, and adenylate charge. In hepatocytes from LPS-injected rats, the oxidation of D-glucose is first increased 2 h after administration of the toxin, despite close-to-normal phosphorylation of the hexose. In hepatocytes prepared from rats killed 24 h after injection of LPS, the phosphorylation of D-glucose, its incorporation into glycogen, and its oxidation are all severely impaired. This sequence of changes, which coincides with a decreased ratio between pyruvate and lactate production from exogenous D-glucose, is comparable to that found with agents that uncouple oxidative phosphorylation. The injection of LPS also alters the metabolic response of hepatocytes to the dimethyl ester of succinic acid (SAD), in terms, for instance, of the sparing action of the ester upon both the production of 14CO2 by hepatocytes prelabeled with L-[U-14C] glutamine and the output of NH4+, and its inhibitory action on glycogenolysis and futile cycling in the reactions catalyzed by glucokinase and glucose-6-phosphatase. Nevertheless, the infusion of SAD protects the rats against the deleterious effect of LPS upon such variables as the plasma concentration of free fatty acids and beta-hydroxybutyrate, the liver ATP content, and the oxidation of D-glucose, as well as the pyruvate/lactate ratio, in hepatocytes prepared from the LPS-injected rats. The infusion of SAD also virtually suppresses lethality in the LPS-injected animals. It is proposed, therefore, that the infusion of succinic acid esters may represent a novel therapeutic approach in endotoxemia and multiple-organ failure.

Adenine Nucleotides↗

Effectiveness of hyperthermia and radiation treatments for patients with esophageal cancer predicted by the succinate dehydrogenase inhibition test.

We used in vitro succinate dehydrogenase inhibition test (SDI test) to predict the combined effects of hyperthermia and irradiation on specimens of esophageal cancer obtained at endoscopy. The mean activity of succinate dehydrogenase (SD) after combined treatment of 6 Gy of irradiation and 43.0 degrees C for 20 hours of hyperthermia was significantly decreased compared to findings with each single treatment (to irradiation; p < 0.01, to hyperthermia; p < 0.05). A correlation between the SD activity and the clinical remedial value was also examined in tissues from 47 patients with esophageal cancer, and treated with hyperthermia and irradiation, in combination. The clinical effect, determined radiographically, showed a correlation of 76.6%. Thus, hyperthermia plus irradiation is effective clinical treatment and the SDI test facilitates prediction of the outcome of this combined treatment.

Carcinoma, Squamous Cell↗