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)

A bovine calf lens epithelial cell line (CLE-1) that synthesizes crystallin has been established in culture and some of its transport properties have been characterized using both cells and membrane vesicles derived from them. The membrane vesicles fractionate with high recovery of plasma membrane markers, showing a 40-fold purification of 5'-AMPase and a 20-fold decrease in the specific activity of the mitochondrial marker enzyme succinic dehydrogenase relative to a cell homogenate. Transport sites demonstrated higher specific activity than has been seen in vesicles from cell lines studied previously. The uptake of alpha-amino isobutyric acid (AIB) (an alanine analog) by CLE-1 cells is stimulated four- to fivefold by Na+ and exhibits a Km of 5.4 mM with a Vmax of 50 pmoles/min.microgram of cell protein. The uptake of leucine was not Na+ stimulatable. The uptake of AIB by the cells was reduced by 43% at confluence. Thus, the cell density dependent behavior of the uptake of the alanine amino acid family in CLE-1 is similar to that of various fibroblast cells. The Na+ caused a threefold stimulation of AIB uptake in the membrane vesicles, while vesicular uptake of leucine was unaffected by Na+. The uptake of adenine, guanine, uridine, and guanosine was also tested in these vesicles. The substrates were rapidly accumulated, came to a steady state distribution within 1-2 minutes, and were recovered as the unaltered compounds after uptake.
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PMID:Nutrient transport in a bovine lens epithelial cell line. 725 81

Tertiary butyl alcohol and trichloroacetic acid (TCA) are known to be contaminants in drinking water. In order to evaluate the interactive toxicity of t-butyl alcohol (TBA) with TCA, young male Wistar rats were dosed through water at a dose level of TBA (0.5% v/v), 25 ppm TCA and a combined dose of TBA+TCA (0.5% v/v TBA, 25 ppm TCA) for a period of 10 weeks ad libitum and were maintained on normal diet. The control animals received plain water and normal diet. There was remarkable loss of body weight and significantly decreased liver triglycerides in the treatment groups in the order of TBA+TCA, TCA, TBA and increased liver weights were observed. Serum succinate dehydrogenase (SDH) levels were significantly increased in TCA- and TBA+TCA-treated groups. There was no significant change in serum alanine (GPT), aspartate (GOT) aminotransferase, serum alkaline (ALP) and acid (ACP) phosphatase levels as well as liver glutathione (GSH) and liver and serum cholesterol levels in the treated groups. But serum triglycerides, liver glycogen, serum glucose (only in TBA- and TCA-treated animals) were significantly high in the treated groups. Lipid peroxidation measured by diene conjugation was significant in TBA+TCA-treated group and kidney GSH levels were significantly low in the treated groups. These results show that interaction of TBA+TCA does bring about alteration in biochemical parameters which may play a pivotal role in toxic responses on long-term exposure.
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PMID:Administration of subtoxic doses of t-butyl alcohol and trichloroacetic acid to male Wistar rats to study the interactive toxicity. 748 97

Changes in oxidative metabolism were studied in hepatopancreas, muscle, and hemolymph of the edible crab Scylla serrata, exposed to a sublethal concentration (2.5 ppm) of cadmium chloride. A significant decrease in glycogen, total carbohydrates, and pyruvate and an increase in lactate levels in hepatopancreas and muscle were observed. Hemolymph sugar levels were increased in experimental crabs. An increase in phosphorylase suggested increased glycogenolysis during cadmium toxicity. The decrease in lactate dehydrogenase activity and the increase in lactate content indicated reduced mobilization of pyruvate into the citric acid cycle. Krebs cycle enzymes such as succinate dehydrogenase and malate dehydrogenase were found to be decreased, suggesting impairment of mitochondrial oxidative metabolism as a consequence of cadmium toxicity. Glucose-6-phosphate dehydrogenase activity was increased, suggesting enhanced oxidation of glucose by the HMP pathway. Cytochrome-c oxidase and Mg2+ ATPase activity levels decreased, indicating impaired energy synthesis during cadmium stress. Acid and alkaline phosphatase activities increased, suggesting enhanced breakdown of phosphates to release energy in view of impaired ATPase system during cadmium exposure. A significant decrease in protein and free amino acid and an increase in ammonia, urea, and glutamine levels were observed in the tissues during exposure. An increase in protease, alanine aminotransaminase, and aspartate aminotransaminase suggested increased proteolysis and transamination of amino acids. The increase in glutamate dehydrogenase, AMP deaminase, and adenosine deaminase indicated increased ammonia production. The increased arginase and glutamine synthetase suggested the detoxification or mobilization of ammonia toward the production of urea and glutamine. These results suggest that cadmium affects oxidative metabolism and induces hyperammonemia, and crabs switch over their metabolic profiles toward compensatory mechanisms for the survivability in cadmium-polluted habitats.
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PMID:Changes in oxidative metabolism in selected tissues of the crab (Scylla serrata) in response to cadmium toxicity. 753 86

beta-N-Oxalylamino-L-alanine (L-BOAA), a non-protein neuroexcitatory amino acid present in the seeds of Lathyrus sativus (chickling or grass pea), is known to produce its neurotoxic effects by overstimulation of non-N-methyl-D-aspartate receptors, especially alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, at micromolar concentrations. It has recently been reported that L-BOAA selectively inhibits mitochondrial enzyme NADH-dehydrogenase (NADH-DH) in brain slices at subpicomolar concentrations. The present study finds that up to 4 mM concentrations of pure L-BOAA fail to inhibit NADH-DH activity in mouse brain homogenate and isolated brain mitochondria. Two known inhibitors (rotenone and 1-methyl-4-phenylpyridinium ion, MPP+) of this mitochondrial enzyme produced significant inhibition under identical conditions. NADH-DH inhibition was also not observed in the homogenate or mitochondria from the brains of animals systemically treated with convulsive doses of L-BOAA. Some inhibition (20-37%) of NADH-DH activity was observed in mouse brain slices incubated with 100-1,000 microM concentrations of L-BOAA for 1 h at 37 degrees C in an atmosphere of 95% O2 and 5% CO2, but the inhibition was nonselective, because the activity of another mitchondrial enzyme, succinic dehydrogenase, was similarly inhibited by L-BOAA. These results are in contrast with the report that L-BOAA inhibits mitochondrial NADH-DH selectively at subpicomolar concentrations. We suggest the observed nonselective NADH-DH inhibition in mouse brain slices treated with L-BOAA is caused by neuronal damage through an excitotoxic mechanism.
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PMID:Action of beta-N-oxalylamino-L-alanine on mouse brain NADH-dehydrogenase activity. 756 83

The biochemical integrity of hepatocellular mitochondria was investigated in rats treated with small doses of human recombinant tumor necrosis factor-alpha (Hur-TNF;50-100 micrograms/kg/d injected intraperitoneally for 5 d) by measuring the activities of three mitochondrial enzymes, glutamate dehydrogenase, succinate dehydrogenase and malate dehydrogenase. The activity of glutamate dehydrogenase (a mitochondrial matrix enzyme) was 20% to 34% lower than that of control rats (P = 0.02 to 0.0003). The activities of succinate dehydrogenase (an inner mitochondrial membrane enzyme) and malate dehydrogenase (a mitochondrial matrix and cytosolic enzyme) showed no significant difference. The effect of TNF on serum amino acid composition was studied using pair-fed, weight-matched partners to eliminate any effect of the reduction of food intake due to TNF treatment. The results for the TNF-treated rats showed a significant (P < 0.05) increase in the concentration of 12 of the 21 amino acids measured (range = 33% to 140%). Of these, major increases were observed in the urea cycle intermediates, ornithine (140%) and arginine (59%), as well as proline (94%), alanine (41%), valine (61%), leucine (64%), isoleucine (63%), and aspargine (71%). Since previous studies have shown that the treatment of rats with the same low doses of TNF did not cause any change in mitochondrial ultrastructure detectable by electron microscopy, these results suggest that significant biochemical changes in amino acid metabolism occur as a result of a decrease in mitochondrial glutamate dehydrogenase activity.
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PMID:Hepatic mitochondrial enzyme activity and serum amino acid composition in rats treated with tumor necrosis factor. 786 40

In rat hepatocytes exposed to [2-13C]pyruvate, newly formed glucose was more efficiently labeled in the carbon C5 than C2, as well as in the carbon C6 than C1, suggesting enzyme-to-enzyme channeling of D-glyceraldehyde 3-phosphate between glyceraldehyde-3-phosphate dehydrogenase and phosphofructoaldolase. Likewise the C1/C2 and C6/C5 ratios for 13C abundance in newly formed glucose, which largely exceeded the C3/C2 ratio of lactate or alanine and could reflect reversibility in the fumarase reaction, were compatible with the enzyme-to-enzyme tunneling of symmetrical Krebs cycle intermediates in the sequence of reactions catalyzed by succinyl-CoA synthetase, succinate dehydrogenase, and fumarase. This study further indicates that the major fraction of pyruvate is metabolized via pyruvate carboxylase rather than pyruvate dehydrogenase.
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PMID:D-glucose generation from [2-13C]pyruvate in rat hepatocytes: implications in terms of enzyme-to-enzyme channelling. 880 44

Decreased glutamine availability is proposed as a mechanism for changes in immune function with intense exhaustive exercise. Less is known about the immunomodulatory effects of regular nonexhaustive exercise. To determine the effects of low intensity regular exercise and dietary glutamine supplementation on plasma glutamine concentrations, lymphocyte metabolism, and immune function, male (278 +/- 5 g) and female (182 +/- 1 g) Sprague-Dawley Buffalo rats were fed nutritionally complete casein-based semi-purified diets +/- 2% w/w glutamine. Rats were trained (21 d), as confirmed by higher (P < 0.05) succinate dehydrogenase activity in soleus muscle, to swim 2 or 4 h.d-1 or remained sedentary. Exercise lowered plasma concentrations of tryptophan, glutamate, methionine, alanine, threonine, aspartate, asparagine, and ornithine and increased the lysine concentration (P < 0.05). Neither diet nor exercise altered plasma glutamine concentrations, lymphocyte phenotypes in spleen, or the in vitro rates of splenocyte energy metabolism (production of glucose and glutamine metabolites or ATP concentrations in the incubation media). Compared with nonsupplemented rats, splenic cytolytic activity (lysis of 51Cr labeled YAC-1 cells) was reduced (P < 0.05) in the glutamine-supplemented exercising group. Under these conditions, glutamine supplementation does not appear to provide any added benefit to the exercise-trained animal.
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PMID:Dietary L-glutamine does not improve lymphocyte metabolism or function in exercise-trained rats. 910 29

The effect of various metabolic inhibitors on the rate of oxygen consumption by procyclic culture forms of Trypanosoma congolense utilizing proline as substrate was investigated. Cyanide inhibited the rate of oxygen consumption by 81.0 +/- 6.7%, malonate inhibited the rate by 51.6 +/- 1.6% and Antimycin A by 73.1 +/- 5.9%. A combination of cyanide and malonate inhibited the rate of oxygen consumption by 84.9 +/- 6.7% while a combination of antimycin A and malonate inhibited the rate by 81.6 +/- 7.6%. Rotenone had no effect on the rate of respiration except when the intact cells were first permeabilized by digitonin after which rotenone decreased the rate of respiration by 20-30%. Salicylhydroxamate (SHAM) did not have any effect on the rate of oxygen consumption. Enzymes involved in the catabolism of proline with high activities were: proline dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase, NADP-linked malic enzyme, alanine aminotransferase and malate dehydrogenase. Activities of 1-pyrroline-5 carboxylate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase and NAD-linked malic enzyme were detectable but lower. The end products of proline catabolism were alanine and glutamate. Unlike the case in Trypanosoma brucei brucei aspartate was not detected. Possible pathways of proline catabolism in procyclic culture forms of T. congolense and of electron transfer are proposed.
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PMID:Catabolism of proline by procyclic culture forms of Trypanosoma congolense. 1042 13

Evidence is increasing that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis, a neurodegenerative disease characterized by selective motoneuron death. To study the role of mitochondrial dysfunction in the pathways leading to motoneuron death, we developed an in vitro model of chronic motoneuron toxicity, based on malonate-induced inhibition of complex II in the mitochondrial electron transport chain. Treatment with malonate resulted in a dose-dependent decrease in cellular ATP levels. We observed that motoneurons were significantly more vulnerable to mitochondrial inhibition than control neurons in the dorsal horn. We could reproduce this dose-dependent phenomenon with the complex IV inhibitor sodium azide. The free radical scavenger alpha-phenyl-N-tert-butylnitrone, the AMPA/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione, and riluzole, a drug that is currently used for the treatment of amyotrophic lateral sclerosis, were protective against malonate-induced motoneuron death. Furthermore, the caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and z-Asp-Glu-Val-Asp-fluoromethyl ketone were both protective against malonate toxicity. Our model shows that chronic mitochondrial inhibition leads to selective motoneuron death, which is most likely apoptotic.
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PMID:Chronic mitochondrial inhibition induces selective motoneuron death in vitro: a new model for amyotrophic lateral sclerosis. 1069 48

Succinate dehydrogenase (SDH) deficiency represents a minor cause of Leigh syndrome (LS). Noticeably, the first mutation in a nuclear-encoded respiratory chain component, a mutation in the 5p15 copy of the flavoprotein (Fp) subunit gene of the SDH, was reported 4 years ago in two siblings with LS and SDH deficiency. We now report a new patient with LS and SDH deficiency. Because two copies of the Fp gene are present in the human genome, we first determined the complete structure of these two copies. This allowed us to identify a 1 bp deletion creating a frameshift in the 3q29 copy, confirming that this second copy was a pseudogene. We also sequenced the promoter region of the 5p 15 gene and, in addition, screened for mutations in the patient. Sequencing of the Fp SDH cDNA in the patient only allowed us to identify a heterozygous C to T transition, changing an alanine to a valine in one allele. This transition was found to be heterozygous in the patient's father but was absent from 150 controls. Transfection of the corresponding mutant cDNA into human Fp-deficient cells failed to restore normal SDH activity, confirming the deleterious effect of this mutation. The second allele, inherited from the mother, carried an A to C substitution changing the methionine translation initiation codon to a leucine. This mutant transcript represented only 10% of total Fp transcript suggesting instability of this transcript. So far, profound deficiencies in complex II activity resulting from mutations in the Fp gene of the SDH present only as LS, a striking observation in view of the ubiquitous expression of this typical housekeeping gene in humans.
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PMID:Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. 1074 66


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