Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The activities of enzymes participating in the regeneration of reduced glutathione (GSH), and their subcellular distribution were studied in cultured rat adrenal cells. 2. It has previously been shown that the adrenocorticolytic agent 7-hydroxymethyl-12-methylbenz[a]anthracene (7-hydroxymethyl-12-MBA) causes a drastic and selective oxidation of mitochondrial GSH in rat adrenal cells. Treatment of the adrenal cells with 7-hydroxymethyl-12-MBA, resulted in a minor decrease in the content of cytochrome c oxidase, nicotinamide nucleotide transhydrogenase, isocitrate dehydrogenase and cytosolic GSH reductase, whereas the activity of lactate dehydrogenase and citrate synthase was unaffected. None of these effects were considered to be responsible for the massive oxidation of mitochondrial GSH induced by 7-hydroxymethyl-12-MBA. 3. 1,3-Bis-(2-chloroethyl)-1-nitrosourea (BCNU) was used to obtain rat adrenal cells cultures with inactivated cytosolic and mitochondrial GSH reductase. The oxidation of mitochondrial GSH, induced by 7-hydroxymethyl-12-MBA, was not dramatically enhanced by the inactivation of GSH reductase, indicating that this enzyme was not rate-limiting in the regeneration of GSH. 4. Fractionation of rat adrenal cells with increasing concentrations of digitonin resulted in an earlier release of citrate synthase in cells treated with 7-hydroxymethyl-12-MBA compared with controls. These results may indicate damage to mitochondrial membranes as a result of 7-hydroxymethyl-12-MBA treatment.
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PMID:Effect of 7-hydroxymethyl-12-methylbenz[a]anthracene and 1,3-bis-(2-chloroethyl)-1-nitrosourea on enzyme activities and oxidation of glutathione in cultured rat adrenal cells. 254 26

Using the selective membrane-solubilizing properties of digitonin and a rapid centrifugation method to separate cytoplasmic and mitochondrial components, the metabolic state of mitochondrial glutathione was investigated in isolated rat hepatocytes. Two pools of GSH were released from hepatocytes incubated with increasing concentrations of digitonin. The largest pool (about 85% of cellular total) was released simultaneously with lactate dehydrogenase, the other pool with citrate synthase, indicating cytoplasmic and mitochondrial locations, respectively. The t1/2 of the mitochondrial pool was estimated by linear regression analysis to be 30 +/- 3 h, while the cytoplasmic pool turned over with a t1/2 of about 2 +/- 0.1 h. The rate of incorporation of [35S]methionine or cysteine into the cytoplasmic pool of GSH, when corrected for turnover, was 15 times greater than into the mitochondrial pool. Mitochondrial GSH was not depleted after 60 min with 185 microM diethyl maleate with or without 75 microM bis-1,3-(2-chloroethyl)-1-nitrosourea, a specific inhibitor of glutathione reductase, whereas cytoplasmic levels were reduced to 40% and 10% of control values, respectively. In vivo experiments, using L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid to inactive gamma-glutamyl transpeptidase to limit cysteine formation from plasma GSH, demonstrated that in the absence of label reincorporation, liver glutathione exhibits a biphasic turnover. The rates of decay (half-lives) and percentages of total GSH under these conditions correlate well with the half-lives and pool distribution seen in the mitochondrial and cytoplasmic populations of GSH found in the isolated hepatocytes.
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PMID:Status of the mitochondrial pool of glutathione in the isolated hepatocyte. 706 8

Although endurance training enhances the antioxidant defence of different tissues, information on the effect of sprint training is scanty. We examined the effect of sprint training on rat skeletal muscle and heart antioxidant defences. Male Wistar rats, 16-17 weeks old, were sprint trained on a treadmill for 6 weeks. Total glutathione levels and activities of glutathione peroxidase, glutathione reductase, glutathione S-transferase and superoxide dismutase in heart and various skeletal muscles were compared in trained and control sedentary animals. Lactate dehydrogenase and citrate synthase enzyme activities were measured in muscle to test the effects of training on glycolytic and oxidative metabolism. Sprint training significantly increased lactate dehydrogenase activity in predominantly fast glycolytic muscles and enhanced total glutathione contents of the superficial white quadriceps femoris, mixed gastrocnemius and fast-glycolytic extensor digitorum longus muscles. Oxidative metabolic capacity increased in plantaris muscle only. Compared with the control group, glutathione peroxidase activities in gastrocnemius, extensor digitorum longus muscles and heart also increased in sprint trained rats. Glutathione reductase activities increased significantly in the extensor digitorum longus muscle and heart. Glutathione S-transferase activity was also higher in the sprint trained extensor digitorum longus muscle. Sprint training did not influence glutathione levels or glutathione-related enzymes in the soleus muscle. Superoxide dismutase activity remained unchanged in skeletal muscle and heart. Sprint training selectively enhanced tissue antioxidant defences by increasing skeletal muscle glutathione content and upregulating glutathione redox cycle enzyme activities in fast and mixed fibre leg muscles and heart.
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PMID:Skeletal muscle and heart antioxidant defences in response to sprint training. 889 59

The effect of endurance training on glutathione (GSH) status and antioxidant enzyme system was investigated in skeletal muscle, heart, and liver of female Sprague-Dawley rats pair fed an isocaloric diet. Ten weeks of treadmill training (25 m/min, 10% grade for 2 h/day, 5 days/wk) increased citrate synthase activity in the deep vastus lateralis (DVL) and soleus muscles by 79 and 39%, respectively (P < 0.01), but not in the heart or liver. In DVL, GSH content was increased 33% (P < 0.05) with training, accompanied by a 64% (P < 0.05) increase in glutamate content but no change in cysteine. Trained rats showed a 62 and 27% higher GSH peroxidase (GPX) and superoxide dismutase (SOD) activity, respectively (P < 0.05), in DVL compared with control rats. In contrast, GSH content and glutathione reductase (GR) activity in soleus declined with training (P < 0.05), whereas activities of GPX and SOD remained unchanged. Training did not alter GSH status in the liver or plasma but significantly decreased the GSH-to glutathione disulfide ratio in the heart. In addition, GR activity in the liver and GSH sulfur-transferase activity in the heart and DVL were significantly lower in the trained vs control rats DVL muscle had threefold higher gamma-glutamyl transpeptidase activity compared with other tissues; however no significant alteration was observed in the activity of gamma-glutamyltranspeptidase or gamma-glutamylcysteine synthetase in the liver, heart, or skeletal muscle. These data indicate that endurance training can cause tissue- and muscle fiber-specific adaptation of antioxidant systems and that GSH homeostasis in extrahepatic tissues may be determined by utilization and uptake of GSH via the gamma-glutamyl cycle.
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PMID:Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific. 903 30

Examination of the ways side-chain carboxylate and amide groups in high-resolution protein crystal structures form hydrogen bonds with main-chain atoms reveals that the most common category is a two-hydrogen-bond four to five residue motif with an aspartate or asparagine (Asx) at the first residue, for which we propose the name Asx-motif. Similar motifs with glutamate or glutamine residues at that position are rare. Asx-motifs occur typically as (1) a common feature of the N termini of alpha-helices called the Asx N-cap motif; (2) an independent motif, usually a beta-turn with an appropriately hydrogen-bonded Asx as the first residue; and (3) a motif incorporated in a beta-bulge loop. Asx-motifs are common, there being just under two-and-a-half in an average-sized protein subunit; of these, about 55 % are Asx N-cap motifs. Because they occur often in many situations, it seems that these motifs have an inherent propensity to form on their own rather than just being a feature stabilised at the end of a helix. Asx-motifs also occur in functionally interesting situations in aspartyl proteases, citrate synthase, EF hands, haemoglobins, lipocalins, glutathione reductase and the alpha/beta hydrolases.
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PMID:A natural grouping of motifs with an aspartate or asparagine residue forming two hydrogen bonds to residues ahead in sequence: their occurrence at alpha-helical N termini and in other situations. 1006 20

Given the potential of reactive oxygen species to damage intracellular proteins during subsequent bouts of muscle contractions, it was suggested that, when this production exceeds the antioxidant capacity, the preexisting antioxidant pathways may be complemented by the synthesis of the defense mechanism represented by heat shock proteins (HSPs), stress proteins with the function of repair and maintaining protein folding. To test this hypothesis, we analyzed reactive carbonyl derivatives in plasma and the expression of HSP72 and activities of enzymes from the oxidative and antioxidant defense systems in the soleus muscle of sedentary rats and rats trained by two protocols: continuous and intermittent. We analyzed all three groups at rest and 2 h after acute exercise. After 8 wk of training, the animals from both groups clearly demonstrated higher resistance to exercise. Both trained groups showed significantly higher citrate synthase, catalase, and glutathione reductase activities than the control group (P < 0.01). After acute exercise, catalase and glutathione reductase activities significantly decreased (P < 0.01) and plasma reactive carbonyl derivatives significantly increased (P < 0.05) in the sedentary group, suggesting an oxidative-stress condition as responsible for exhaustion in this group. Finally, after acute exercise, the induction of HSP72 expression occurred only in the sedentary group, suggesting that HSP72 acts as a complementary protective mechanism in exercise-induced oxidative stress.
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PMID:HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats. 1104 34

The aim of this work was to evaluate the effects of prolonged starvation and refeeding on antioxidant status and some metabolic-related parameters in common dentex (Dentex dentex) liver. Fish deprived of food for 5 weeks showed a significant increase in lipid peroxidation, measured as malondialdehyde (MDA) levels. The activity of the antioxidative enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in starved fish significantly increased (by 42%, 22%, and 52%, respectively), whereas glutathione reductase (GR) activity was significantly depressed by 53% compared to controls. No qualitative changes in the SOD isoenzymatic pattern were detected by nondenaturing PAGE analysis, but the isoforms corresponding to CuZn-SOD I and II were enhanced in starved fish. The activity of the enzymes indicative of oxidative metabolism, beta-hydroxyacyl CoA dehydrogenase (HOAD) and citrate synthase (CS), significantly increased (by 123% and 28%, respectively), and that of glucose-6-phosphate dehydrogenase (G6PDH) was inhibited by 56%. Oxidative damage under these circumstances is reversible since all biomarkers assayed returned to control values after refeeding. Our results show that prolonged starvation leads to a pro-oxidant situation and oxidative stress despite activation of antioxidant defense mechanisms, and that inhibition of G6PDH activity might be responsible for this failure in cellular antioxidant defenses.
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PMID:Oxidative stress and antioxidant defenses after prolonged starvation in Dentex dentex liver. 1555 78

Indole acetic acid (IAA) is an auxin and can be synthesized in animals. This compound is metabolized in vitro by peroxidase, producing reactive oxygen species. The toxic effect of indole acetic acid in leukocytes is associated with peroxidase activities and these processes have been implicated in activation of glucose and glutamine metabolism. However, studies in vitro have shown that IAA, in absence of peroxidase, is an antioxidant almost as high in potency as those of other indolic compounds. The purpose of this study was to investigate the possible involvement of a toxic effect of indole acetic acid in the liver, as evidenced by oxidative stress and enzyme activities of the glucose pathway. The animals received IAA by subcutaneous or gavage administration in a phosphate buffered saline (the control group received only the phosphate buffered saline). The other groups received IAA at concentrations of 1 mg, 18 mg and 40 mg per kg of body mass per day. Treatments with 18 mg and 40 mg IAA decreased the activity of catalase by both subcutaneous (30% and 26%) or gavage administration (19% and 28%), respectively. A similar effect was observed on the activity of glutathione peroxidase of animals exposed to 18 mg and 40 mg IAA: A decrease of 34% and 29%, respectively, for subcutaneous administration and a decrease of 29% and 25%, respectively, for gavage administration. However, in neither source of administration did the acid alter superoxide dismutase, glutathione reductase and myeloperoxidase activities. Another alteration was observed in respect of reduced glutathione content in this organ. The lipid peroxidation level showed a significant decrease with subcutaneous (30%, 29% and 24%) and gavage administration (25%, 26% and 24%) using 1 mg, 18 mg and 40 mg of IAA, respectively compared with the control. The reduced glutathione content and catalase activity in the plasma were not altered by either of the two methods of administration. In addition to these findings, after subcutaneous or gavage administration of IAA, the activities of hepatic enzymes of glucose metabolism were not affected (glucokinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase and citrate synthase). Evidence is presented herein that IAA did not have a pro-oxidant effect in the liver as deduced from a reduction of catalase and glutathione peroxidase activities, a decrease of lipid peroxidation content and no alteration of the pool of reduced glutathione. The effects of IAA were independent of the way of administration.
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PMID:Influence of indole acetic acid on antioxidant levels and enzyme activities of glucose metabolism in rat liver. 1631 62

Oxidative stress during cardiac arrest may inactivate myocardial enzymes and thereby exacerbate ischemic derangements of myocardial metabolism. This study examined the impact of cardiac arrest on left ventricular enzymes. Beagles were subjected to 5 min of cardiac arrest and 5 min of open-chest cardiac compressions (OCCC) before epicardial direct current countershocks were applied to restore sinus rhythm. Glutathione/glutathione disulfide redox state (GSH/GSSG) and a panel of enzyme activities were measured in snap-frozen left ventricle. To test whether oxidative stress during arrest inactivated the enzymes, metabolic (pyruvate) or pharmacological (N-acetyl-l-cysteine) antioxidants were infused intravenously for 30 min before arrest. During cardiac arrest, activities of phosphofructokinase, citrate synthase, aconitase, malate dehydrogenase, creatine kinase, glucose-6-phosphate dehydrogenase, and glutathione reductase fell by 56, 81, 55, 34, 42, 55, and 45%, respectively, coincident with 50% decline in GSH/GSSG. OCCC effected full recovery of glutathione reductase and partial recovery of citrate synthase and aconitase, in parallel with GSH/GSSG. Phosphofructokinase, malate dehydrogenase, creatine kinase, and glucose-6-phosphate dehydrogenase recovered only after cardioversion. Antioxidant pretreatments augmented phosphofructokinase, aconitase, and malate dehydrogenase activities before arrest and enhanced these activities, as well as those of citrate synthase and glucose-6-phosphate dehydrogenase, during arrest. In conclusion, cardiac arrest reversibly inactivates several important myocardial metabolic enzymes. Antioxidant protection of these enzymes implicates oxidative stress as a principal mechanism of enzyme inactivation during arrest.
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PMID:Oxidative stress reversibly inactivates myocardial enzymes during cardiac arrest. 1692 Aug 3

Overreaching (OVR) is defined as the initial phase of overtraining syndrome and is known as a metabolic imbalance leading to short-term fatigue. Exercise increases reactive oxygen species production, which can oxidize intracellular structures impairing cell function and thus leads to OVR process. The aim of this work is to study the behavior of oxidative stress markers in subjects submitted to an OVR protocol. Thirty rats were divided in exercise and control group, and submitted to an 8-week-endurance training (ET) and a 3-week-OVR protocol. Thiobarbituric acid reactive substances (TBARs), reactive carbonylated derivatives (RCD), glutathione reductase (GR), catalase (CAT) and citrate synthase (CS) activities and stress protein HSP72 were measured in soleus (SO), extensor digital longus (EDL) and semitendinuous (ST) muscles. ET induced significant enhancement (P<0.05) in CS, GR, CAT, TBARs, RCD and HSP72 in SO, EDL and ST. OVR induced higher levels (P<0.05) of TBARs, RCD and HSP72 compared with ET only in SO, while in EDL and ST all measured parameters ranged at same levels reached during ET. We concluded that stress-induced OVR protocol is fiber type dependent, the SO muscle fiber type I being the most affected by this treatment.
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PMID:Overreaching-induced oxidative stress, enhanced HSP72 expression, antioxidant and oxidative enzymes downregulation. 1734 86


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