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)

Using isolated rat hepatocytes the biochemical effects of hydrazine have been investigated using both conventional assay techniques and high resolution proton NMR. High resolution proton NMR revealed that hydrazine caused a significant increase in alanine and lactate levels in the incubation buffer, whereas levels of beta-hydroxybutyrate were decreased. NMR also detected metabolites of hydrazine notably acetylhydrazine and a cyclised hydrazone formed with alpha-ketoglutarate. Changes were detected in NADH and NADPH, ATP, succinate dehydrogenase (SDH) and total non-protein sulphydryl groups (TNPSH). However, the changes in pyridine nucleotides occurred at higher concentrations than those affecting succinate dehydrogenase and ATP. Similarly, the depletion of TNPSH occurred at a higher concentration and with a different time course to that seen with ATP depletion and inhibition of succinate dehydrogenase.
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PMID:A biochemical and NMR spectroscopic study of hydrazine in the isolated rat hepatocyte. 133 60

By reaction of spermidine trihydrochloride with K2PdCl4 and PdCl2 at different pH's, we have synthesized the [sperH3]2[PdCl4]3 (I), [PdCl2(sperH)]2[PdCl4] (II), and [(PdCl2)3(sper)2] (III) compounds. The structure of these compounds was studied by IR and 1H NMR; complex II was analyzed by x-ray diffraction. In this complex the spermidine is attached to the PdCl2 group forming a six-member chelate ring with a protonated terminal amine group. The crystal of [PdCl2(sperH)]2[PdCl4] x 2H2O (II) is monoclinic, P2(1)/n, with a = 7.023(1) A, b = 12.662(1) A, c = 18.435(3) A, and beta = 99.95(1) degrees, Z = 4, R = 0.051, and Rw = 0.058 on the basis of 2690 independent reflections. We have compared the antitumor activity in vitro against the isolated human breast carcinoma MDA-MB 468 cell line of compounds I, II, and III with that of cis-diamminedichloroplatinum(II), cis-DDP. The results show that compounds III and III have values of ID50 similar (0.74 microgram/ml) or even lower (0.56 microgram/ml) than cis-DDP (0.80 microgram/ml). We also observed that compounds I, II, and III have the ability to induce conformational changes in covalently closed circular (ccc) form of the pUC8 plasmid DNA. Compounds II and III also induce conformational changes in the open circular (oc) form of this plasmid.
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PMID:Palladium(II) salt and complexes of spermidine with a six-member chelate ring. Synthesis, characterization, and initial DNA-binding and antitumor studies. 140 77

A series of 6,8-disubstituted 3-[5- [[2-hydroxy-3-[(substituted phenyl)amino]propyl]thio]-1,3,4-thiadizol-2-yl] 2-methyl-4(3)- quinazolinones were synthesized whose structures were confirmed by elemental analyses, IR, NMR and mass spectral studies. All these compounds were evaluated in vivo for anticonvulsant and analgesic activities and in vitro for monoamine oxidase and succinate dehydrogenase enzyme inhibitory activities using rat brain homogenate as a source of enzyme at final concentration of 1 x 10(-4) mol/l. ALD50 values indicated their relatively nontoxic nature.
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PMID:Substituted quinazolones as potent anticonvulsants and enzyme inhibitors. 189 22

Oxidation of [3-13C]propionate was studied in cultured yeast cells, and the distribution of label in the 2- and 3-positions of alanine was detected by 13C NMR. [3-13C]Propionate forms [2-13C]succinyl-CoA in the mitochondria which then enters the citric acid cycle and forms malate through two symmetrical intermediates, succinate and fumarate. If these symmetrical intermediates randomly diffuse from one enzyme to the next in mitochondria as is normally assumed, then 13C labeling in malate C2 and C3 must be equal. However, any direct transfer of metabolites from site to site between succinate thiokinase, succinate dehydrogenase, and fumarase would result in an uneven distribution of 13C in malate C2 and C3 and any molecules derived from malate. Since pyruvate may be derived from malate via the malic enzyme and subsequently converted into alanine by transamination, any 13C asymmetry in alanine C2 and C3 must directly reflect the 13C distribution in the malate pool. During oxidation of [3-13C]propionate, we detect a significant quantity of labeled alanine, where 13C enrichment in C3 is significantly higher than that in C2. Inhibition of succinate dehydrogenase with malonate or creating conditions that increase the chances of a back-reaction (from malate to fumarate) result in a significant decrease in the asymmetric labeling of alanine. Ubiquinone-deficient yeast cells (having only 10% of the oxidative capacity of wild-type cells) could slowly oxidize propionate, but in this case the 13C labeling was equal in the C2 and C3 of alanine, showing that isotope randomization had occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Channeling of TCA cycle intermediates in cultured Saccharomyces cerevisiae. 212 73

Exposure of rats to static magnetic field 1 hour daily for a period of 7 weeks (7 days a week) leading to disturbances of the respiration processes in the mitochondria of liver cells. The rate of respiration through NADH dehydrogenase, succinic dehydrogenase and cytochrome oxidase was dependent on both the duration and the intensity value of the field applied. The animals showed greater sensitivity to the action of a 0.008 T magnetic induction field than to that of 0.15 T. The observed changes were reversible after 3 months since the everyday exposure had been stopped.
Physiol Chem Phys Med NMR 1986
PMID:Effect of magnetic field on the process of cell respiration in mitochondria of rats. 302 16

The interaction of the mutagenic dye 9-aminoacridine (9AA) with the self-complementary tetranucleotide dpApGpCpT has been studied by a combination of proton NMR titrations and thermal denaturation experiments. A minimum of three complexes of well-defined stoichiometry can be demonstrated in this system. Complex I is a 1:2 9AA/tetranucleotide structure occurring in the presence of excess tetranucleotide. The dye appears to intercalate within the GpC/GpC site of a tetranucleotide duplex. Complex II is a 2:2 9AA/tetranucleotide structure, with two dyes intercalated at the ApG/CpT sites of the duplex. Complex III is a low-temperature 4:2 9AA/tetranucleotide structure containing two dye molecules stacked over the terminal A-T residues of the duplex in addition to those present in complex II. These results show that both sequence selectivity and site exclusion can occur in this model system.
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PMID:Site exclusion and sequence specificity in binding of 9-aminoacridine to the deoxytetranucleotide dpApGpCpT. 693 59

The effects of 3-nitropropionic acid (3-NPA), an inhibitor of succinate dehydrogenase, on cerebral metabolism were investigated in mice by NMR spectroscopy. 3-NPA, 180 mg/kg, caused a dramatic buildup of succinate. Succinate was labeled 5.5 times better from [1-(13)C]glucose than from [2-(13)C]acetate, showing a predominantly neuronal accumulation. [1-(13)C]Glucose labeled GABA in the C-2 position only, compatible with inhibition of the tricarboxylic acid (TCA) cycle associated with GABA formation, at the level of succinate dehydrogenase. Aspartate was not labeled by [1-(13)C]glucose in 3-NPA-intoxicated animals. In contrast, [1-(13)C]glucose labeled glutamate in the C-2, C-3, and C-4 positions showing uninhibited cycling of label in the TCA cycle associated with the large, neuronal pool of glutamate. The labeling of glutamine, and hence GABA, from [2-(13)C]acetate showed that the TCA cycle of glial cells was unaffected by 3-NPA and that transfer of glutamine from glia to neurons took place during 3-NPA intoxication. The high 13C enrichment of the C-2 position of glutamine from [1-(13)C]glucose showed that pyruvate carboxylation was active in glia during 3-NPA intoxication. These findings suggest that 3-NPA in the initial phase of intoxication fairly selectively inhibited the TCA cycle of GABAergic neurons; whereas the TCA cycle of glia remained uninhibited as did the TCA cycle associated with the large neuronal pool of glutamate, which includes glutamatergic neurons. This may help explain why the caudoputamen, which is especially rich in GABAergic neurons, selectively undergoes degeneration both in humans and animals intoxicated with 3-NPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective inhibition of the tricarboxylic acid cycle of GABAergic neurons with 3-nitropropionic acid in vivo. 764 96

An 11-year-old girl with exercise intolerance, fatiguability from early childhood, had high blood lactate levels. Histochemistry showed increased activity of succinate dehydrogenase at the periphery of the muscle fibres, whereas aggregates of mitochondria were seen by electron microscopy. Biochemical investigation of isolated mitochondria and homogenate from muscle showed evidence of a severe complex I deficiency. In contrast, succinate dehydrogenase, complex II+III and complex IV were increased in activity. Therapy with biotin, riboflavin, nicotinamide, carnitine and amino acids resulted in an improvement of her endurance. 31P NMR spectroscopy of her forearm muscle showed a decreased ratio of phosphocreatine (PCr) over ATP. After exercise the PCr recovery rate was 26% of the average rate in 20 healthy untrained controls. When the therapy was suspended the PCr/ATP ratio at rest decreased from 2.60 to 2.34, and the PCr recovery rate after exercise decreased to 21% of the average control rate. The therapy was reinstituted but only riboflavin and carnitine were given. The PCr/ATP ratio increased to 2.60 and the PCr recovery rate increased to 32% of the control rate. Improvement of the energy metabolism in patients with defects in the oxidative phosphorylation may add to the quality of life; 31P NMR spectroscopy can measure these improvements.
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PMID:Vitamin-responsive complex I deficiency in a myopathic patient with increased activity of the terminal respiratory chain and lactic acidosis. 796 74

The structures of the physical complex of d(GCGT).d(ACGC) with the anthracycline antitumor drug nogalamycin were studied in order to determine the sequence specificity and the drug orientation at the symmetric d(C2G3).d(C6G7) binding site of this oligonucleotide. For this purpose, one- and two-dimensional NMR techniques were used in combination with molecular mechanics and molecular dynamics computations. Analysis of the NMR spectra reveals that nogalamycin forms two different intercalation complexes with d(GCGT).d(ACGC). These complexes are called complex I and complex II and are present in a ratio of 0.45:0.55. In both complexes the nogalamycin is intercalated at the d(C2G3).d(C6G7) sequence with the bicyclic and nogalose sugars residing in the major and minor groove, respectively. This results in a buckling of the flanking base pairs and a doubling of the inter-base-pair distances at the intercalation site. In complex I, the aglycon ring of the drug stacks with the C6-G7 bases, and the sugars are directed to the G1.C8 end; while in the case of complex II the anthraquinone ring system is stacked with C2-G3 bases, and the sugars are pointed to the T4.A5 base pair end. The two nogalamycin-d(GCGT).d(ACGC) structures are stabilized by intra- and intermolecular hydrogen bonds, electrostatic interactions, and van der Waals contacts. Comparison of different nogalamycin-oligonucleotide structures reveals a nogalamycin binding specificity to the 3'-side of the cytosine base in cytosine-purine sequences in double-stranded DNA.
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PMID:The antitumor drug nogalamycin forms two different intercalation complexes with d(GCGT).d(ACGC). 843 47

The generation of 13C-labelled lactate by colon carcinoma cells of the Caco-2 line incubated for 120 min in the presence of [2-13C]propionate (10 mM) was assessed by 13C NMR. About 10% of the total amount of 13C-labelled lactate was recovered in the cell pellet and displayed a [2-13C]lactate/[3-13C]lactate isotopomer ratio of 1.18 +/- 0.01. An even higher isotopomer ratio of 1.53 +/- 0.14 was observed in the case of 13C-labelled lactate released by the cells into the incubation medium. These findings indicate that, in the Caco-2 cells, metabolic intermediates of the Krebs cycle undergo enzyme-to-enzyme channelling in the sequence of reactions catalysed by succinyl-CoA synthetase, succinate dehydrogenase and fumarase.
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PMID:Enzyme-to-enzyme channelling of Krebs cycle metabolic intermediates in Caco-2 cells exposed to [2-13c]propionate. 876 Mar 74


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