Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to locate sites of action of thyroid hormone on mitochondrial oxidative phosphorylation we have used an experimental application of control analysis as previously described [Groen, Wanders, Westerhoff, Van der Meer & Tager (1982) J. Biol. Chem. 257, 2754-2757]. Rat-liver mitochondria were isolated from hypothyroid rats or from hypothyroid rats 24 h after treatment with a single dose of 3,3',5-triiodothyronine (T3). The amount of control exerted by four different steps on State-3 respiration with succinate as respiratory substrate was quantified by using specific inhibitors. The hormone treatment resulted in an increase in the flux control coefficient of the adenine nucleotide translocator, the dicarboxylate carrier and cytochrome c oxidase and a decrease in the flux control coefficient of the bc1-complex. The results of this analysis indicate that thyroid hormone treatment results in an activation of the bc1-complex and of at least one other enzyme, possibly succinate dehydrogenase. Measurement of the extramitochondrial ATP/ADP ratio at different rates of respiration (induced by addition of different amounts of hexokinase in the presence of glucose and ATP) showed that the adenine nucleotide translocator operates at a higher (ATP/ADP)out after T3 treatment, which supports previous reports on stimulation of this step by thyroid hormone.
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PMID:Effects of thyroid hormone on mitochondrial oxidative phosphorylation. 397 64

Siccanin at 3 mug/ml completely inhibited the growth of Trichophyton mentagrophytes. The primary site of action of siccanin on T. mentagrophytes is succinate dehydrogenase in the terminal electron transport system. At a concentration of siccanin giving 50% inhibition of growth (0.3 mug/ml), respiration of intact cells was inhibited more strongly than any other cellular functions tested, including the syntheses of cellular ribonucleic acid, deoxyribonucleic acid, phospholipid, protein, and cell wall fractions. In addition, at the same concentration siccanin did not cause any detectable damage in the permeability of the cells. Furthermore, the oxidation of succinate in mitochondrial preparation is more sensitive to the antibiotic than respiration in intact cells. Oxidation of other substrates tested was less sensitive to siccanin than that of succinate. The antibiotic inhibited both phosphorylation and oxidation, without causing changes in the P:O ratio. Siccanin at 0.03 mug/ml, which caused 50% inhibition of succinate oxidation in mitochondria, had effect neither on the exchange reaction between inorganic phosphate (P(i)) and adenosine triphosphate (ATP) nor on that between adenosine diphosphate and ATP. An ATP phosphohydrolase activity was also insensitive to the antibiotic. At very high concentrations, however, the antibiotic slightly inhibited the P(i)-ATP exchange reaction. From those results, it was concluded that siccanin inhibits fungal growth by inhibiting the respiratory electron transport system.
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PMID:Mode of action of the antibiotic siccanin on intact cells and mitochondria of Trichophyton mentagrophytes. 425 Jun 9

1. Changes in the amounts and distribution of protein and respiratory enzymes have been estimated during the life cycle of the fly Lucilia cuprina. 2. The fully fed larva contains about 7mg. of protein, the pupa and newly emerged fly about 4mg., and the mature adult about 3mg. 3. There are two periods of incorporation of protein into particles at the expense of the soluble protein; the first, immediately after pupation, may store protein (0.5mg./insect) for use in adult development; the second, over the period of emergence, was due mainly to the development of the thoracic mitochondria of the adult (0.7mg./insect). 4. In the thorax, cytochrome c oxidase and the dehydrogenases for glycerophosphate, isocitrate (NAD-dependent), succinate and malate appeared initially in small particles (less than 1mu in diameter). 5. In adult development these enzymes were redistributed so that in the mature fly most of the activity was present in larger particles (1-10mu in diameter). 6. During this redistribution the specific activity (mul. of oxygen/hr./mg. of protein) of glycerophosphate dehydrogenase in the small particles was 690 at 1(1/2) days before emergence, 955 at emergence and 980 at 7 days after emergence; the corresponding values for the large particles were 164, 760 and 1220. 7. In the mature fly the highest specific activities (mul. of oxygen/hr./mg. of protein) estimated were: glycerophosphate dehydrogenase 1380, isocitrate dehydrogenase (NAD-dependent and requiring ADP and Mg(2+)) 408, succinate dehydrogenase 122, malate dehydrogenase 190, and cytochrome c oxidase 1360. 8. The results are considered in relation to the development of the flight-muscle sarcosomes.
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PMID:Aspects of the development of flight-muscle sarcosomes in the sheep blowfly, Lucilia cuprina, in relation to changes in the distribution of protein and some respiratory enzymes during metamorphosis. 429 61

The effect of chronic ethanol intoxication on oxidative phosphorylation in the rat brain mitochondrial fraction was examined. Moreover, electron microscopy was used to verify the quantitative composition of the fraction and for examination of ultrastructural changes in the mitochondria. The experiments were carried out with 60 rats receiving, beside the normal diet, ethyl alcohol according to a modified RATCLIFFE model. In isolated rat brain mitochondria the NAD-dependent oxidation of substrates (glutamate + malate) was decreased. The phosphorylation index ADP/0 and the respiratory control ratio (RCR) in rat brain mitochondria from ethanol-treated rats were unchanged in the presence of both succinate and glutamate + malate. Chronic ethanol feeding did not induce any changes of succinate dehydrogenase and cytochrome oxidase activities in solubilised mitochondria fractions of rat brain. Electron microscopy studies revealed that mitochondria from control animals retained their outer and inner membranes, whereas those from rats given ethanol were almost always swollen and some were disrupted. In mitochondrial fractions isolated from ethanol-intoxicated rats an increase was observed of contaminating elements i.e. axons and synaptosomes of various sizes. It should be stressed that the mitochondria located inside synaptosomes and axons were unchanged. The composition of the fractions was quantitatively evaluated and confirmed the diminution of "free" mitochondria in the experimental fractions in favour of "bound" mitochondria which mainly occurred in the synaptosomes with preserved metabolic activity. On the basis of electron microscopy studies it could be suggested that ethanol intoxication causes the damage of some mitochondria, which become more sensitive to mechanical destruction during isolation procedure, and they do not sediment together with the fraction of normal ones. The absence of "free" mitochondria in pellets explains the spurious lack of disturbances in the energy metabolism of brain mitochondria after chronic ethanol intoxication.
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PMID:Ultrastructural and biochemical studies of the brain and other organs in rat after chronic ethanol administration. III. Influence of ethanol intoxication on oxidative phosphorylation of the rat brain mitochondria with ultrastructural and morphometric evaluation of mitochondrial fraction). 624 56

Two experiments were conducted to determine if variations in diet composition sufficient to alter circulating triiodothyronine (T3) concentration would influence hepatic mitochondrial metabolism. In experiment 1, mitochondrial respiration and the activity of succinate dehydrogenase (SDH), cytochrome oxidase (CO) and alpha glycerophosphate dehydrogenase (m alpha-GPD) were measured in 42-day-old male rats fed diets containing casein/carbohydrate/fat: 8/73/10% (low protein), 22/59/10% (control protein), and 45/36/10% (high protein) for 3 weeks. When compared to control, serum T3 was increased 2-3 times in the low and decreased 19% in the high protein-fed groups. Mitochondria isolated from low protein-fed rats consumed less oxygen in both state 4 and state 3 with succinate as substrate when compared to control or high protein fed rats. However, ADP/O and respiratory control (RC) ratios were similar in all groups. Activity of SDH and CO was decreased only in low protein-fed rats. M alpha-GPD activity was increased in the low and decreased in the high protein fed-rats. In experiment 2, alpha-glycerophosphate shuttle activity was increased 2-3 fold and malate-aspartate shuttle activity decreased 60% in intact mitochondria isolated from low protein-fed rats when compared to rats pair-fed control diet. These results suggest a role for diet composition as a regulator of hepatic intermediary metabolism mediated by thyroid hormones.
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PMID:Influence of diet composition on serum triiodothyronine (T3) concentration, hepatic mitochondrial metabolism and shuttle system activity in rats. 625 66

The in vitro effects of PR toxin, a toxic secondary metabolite produced by certain strains of Penicillium roqueforti, on the membrane structure and function of rat liver mitochondria were investigated. It was found that the respiratory control and oxidative phosphorylation of the isolated mitochondria decreased concomitantly when the toxin was added to the assay system. The respiratory control ratio decreased about 60% and the ADP/O ratio decreased about 40% upon addition of 3.1 X 10(-5) M PR toxin to the highly coupled mitochondria. These findings suggest that PR toxin impairs the structural integrity of mitochondrial membranes. On the other hand, the toxin inhibited mitochondrial respiratory functions. It exhibited noncompetitive inhibitions to succinate oxidase, succinate-cytochrome c reductase, and succinate dehydrogenase activities of the mitochondrial respiratory chain. The inhibitory constants of PR toxin to these three enzyme systems were estimated to be 5.1 X 10(-6), 2.4 X 10(-5), and 5.2 X 10(-5) M, respectively. Moreover, PR toxin was found to change the spectral features of succinate-reduced cytochrome b and cytochrome c1 in succinate-cytochrome c reductase and inhibited the electron transfer between the two cytochromes. These observations indicate that the electron transfer function of succinate-cytochrome c reductase was perturbed by the toxin. However, PR toxin did not show significant inhibition of either cytochrome oxidase or NADH dehydrogenase activity of the mitochondria. It is thus concluded that PR toxin exerts its effect on the mitochondrial respiration and oxidative phosphorylation through action on the membrane and the succinate-cytochrome c reductase complex of the mitochondria.
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PMID:Biochemical effects of PR toxin on rat liver mitochondrial respiration and oxidative phosphorylation. 632 85

Rat enterocyte mitochondria were prepared with respiratory control ratios of 4 or 5 and occasionally 6. When EGTA was excluded from the mitochondrial incubation medium the calculated P/O ratios were high, especially those based on the first addition of ADP. These ratios were lowered by increasing the EGTA concentration from 1 mM to 2 mM in the mitochondrial preparation medium and including 1 mM-EGTA in the incubation medium. The use of EDTA in the enterocyte isolation medium led to the mitochondria requiring added cytochrome c. Substituting EGTA for EDTA abolished this requirement. The mitochondrial fraction consisted of two components, an upper cream-coloured layer rich in DNA and a lower brown-coloured layer poor in DNA. Both components were capable of oxidative phosphorylation with succinate or the glutamate/malate couple as substrates. The mitochondrial yield was assessed by assaying succinate dehydrogenase activity, and the contamination of the mitochondrial fraction by other cell organelles was assessed by assays for appropriate marker enzymes.
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PMID:Preparation of rat enterocyte mitochondria. 642 61

Lipid peroxidation in rat brain mitochondria was induced by NADH in the presence of ADP and FeCl3. CV-2619 inhibited the lipid peroxidation in a concentration-dependent manner; the concentration giving 50% inhibition (IC50) was 84 microM. In addition, the inhibitory effect of CV-2619 was strongly enhanced by adding substrates of mitochondrial respiration; when succinate, glutamate, or succinate plus glutamate was added, the IC50 of CV-2619 was changed to 1.1, 10, or 0.5 microM, respectively. Metabolites of CV-2619 also inhibited the lipid peroxidation. The inhibitory effect of CV-2619 on mitochondrial lipid peroxidation disappeared when TTFA, an inhibitor of complex II in mitochondrial respiratory chain, was added. The results indicate that in mitochondria CV-2619 is changed to its reduced form which inhibits lipid peroxidation.
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PMID:Inhibition of lipid peroxidation by a novel compound (CV-2619) in brain mitochondria and mode of action of the inhibition. 651 32

Baboons fed ethanol (50% of total calories) chronically develop ultrastructural alterations of hepatic mitochondria. To determine whether mitochondrial functions are also altered, mitochondria were isolated from nine baboons fed ethanol chronically and their pair-fed controls. At the fatty liver stage, ADP-stimulated respiration was depressed in ethanol-fed baboons by 59.4% with glutamate, 43.2% with acetaldehyde, 45.1% with succinate and 51.1% with ascorbate as substrates. A similar decrease was noted in the ADP/O ratio (14 to 28%) and respiratory control ratio (20 to 44%) with all substrates. Similar alterations of mitochondrial functions were observed in baboons with more advanced stages of liver disease, namely fibrosis. These changes after ethanol treatment were associated with decreases in the enzyme activities of mitochondrial respiratory chain: glutamate, NADH and succinate dehydrogenase (42, 24 and 28%, respectively), glutamate-, NADH- or succinate-cytochrome c reductase (42, 27 and 32%, respectively) and cytochrome oxidase (59.6%). The content of all cytochromes was also decreased in ethanol-fed baboons, especially aa3 (57%). Moreover, [14C]leucine incorporation into mitochondrial membranes was depressed by 21% after ethanol treatment. On the other hand, glutamate dehydrogenase activities of serum and cytosol in ethanol-fed baboons were significantly higher than those in pair-fed controls. Morphologically, mitochondria of ethanol-fed baboons were larger than those of pair-fed controls. However, the mitochondrial protein content per mitochondrial DNA was unchanged. From these results, we conclude that, morphologically and functionally, hepatic mitochondria in baboons are altered by chronic ethanol consumption; it is noteworthy that these changes are fully developed already at the fatty liver stage, and that morphological alteration appears to reflect the damage of mitochondrial membranes rather than an adaptive hypertrophy.
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PMID:Biochemical and morphological alterations of baboon hepatic mitochondria after chronic ethanol consumption. 653 46

Several parameters of oxidative phosphorylation reaction were studied in vitro in isolated liver mitochondria from hypothyroid rats. When succinate was employed as a respiratory substrate for mitochondria incubated in a mannitol/sucrose/phosphate buffer, and measurements were performed during initial additions of ADP, the magnitude of state 3 and state 4 respiration was not different between mitochondria from the hypothyroid and those from the control rats. During the course of repetitive additions of ADP and consequently of sequential transitions from state 4 to state 3 and back to state 4, mitochondria from hypothyroid animals showed a gradual decline in the rate of both state 3 and state 4 respiration whereas those from normal animals did not. The total succinate dehydrogenase activity was not different between the two types of mitochondria, and the decline in state 3 and state 4 respiration was not accompanied by any change in the apparent Km for ADP or in the corrected ADP/O ratio [Biochem. Biophys. Res. Commun. (1973) 53, 988]. The amount of oxygen consumed during the state-4----3----4 transition was lower in the hypothyroid than in the control mitochondria. These alterations were reversed if the hypothyroid animals were injected with thyroxine intraperitoneally (2 micrograms/100 g body weight) for 3 weeks before isolation of mitochondria. These results indicate that the fall of respiratory activity in hypothyroidism may result from the decrease not only of respiratory activities of state 3 and state 4, but also of the energy spent in the process of the state-4----3----4 transition, while the coupling efficiency per se remains normal. These properties become manifest when mitochondria respond to pulses of ADP load, a situation likely to occur in situ.
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PMID:Alterations of oxidative phosphorylation reactions in mitochondria isolated from hypothyroid rat liver. 672 67


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