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:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten obese women with normal glucose tolerance, 10 obese patients with sulphonylurea-treated non-insulin-dependent diabetes (NIDD) and 11 patients with insulin-dependent diabetes (IDD; treated for 3-31 yr) took part in a 10-week programme of physical training in 50-min sessions, 2-3 times a week. As a result of training, maximal oxygen uptake increased significantly by about 18, 13 and 8% in the 3 groups, respectively, and citrate synthase in muscle increased significantly by 27-42%. The lipoprotein-lipase activity in muscle tissue (sampled by a needle-biopsy technique from the lateral vastus muscle) did not change. The number of capillaries/fibre in muscle tissue increased. This was accompanied by an increase in muscle fibre area, resulting in an unchanged number of capillaries/mm2. This may explain why the lipoprotein-lipase activity was unaltered. The latter activity in the group with IDD was lower than was predicted from the number of capillaries/mm2. This number was in fact larger than in the obese and NIDD groups. These results indicate that the increase in capillary density and lipoprotein-lipase activity that occurs in healthy young individuals as an effect of endurance training does not take place in obese, NIDD and IDD patients.
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PMID:Non-response of muscle capillary density and lipoprotein-lipase activity to regular training in diabetic patients. 399 72

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25 degrees C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD-isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP-malate dehydrogenase (11.0), ATP-citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP-isocitrate dehydrogenase (3.7), NAD-malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109mug/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3-6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP-citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.
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PMID:The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. 439 82

1. In epididymal adipose tissue synthesizing fatty acids from fructose in vitro, addition of insulin led to a moderate increase in fructose uptake, to a considerable increase in the flow of fructose carbon atoms to fatty acid, to a decrease in the steady-state concentration of lactate and pyruvate in the medium, and to net uptake of lactate and pyruvate from the medium. It is concluded that insulin accelerates a step in the span pyruvate-->fatty acid. 2. Mitochondria prepared from fat-cells exposed to insulin put out more citrate than non-insulin-treated controls under conditions where the oxaloacetate moiety of citrate was formed from pyruvate by pyruvate carboxylase and under conditions where it was formed from malate. This suggested that insulin treatment of fat-cells led to persistent activation of pyruvate dehydrogenase. 3. Insulin treatment of epididymal fat-pads in vitro increased the activity of pyruvate dehydrogenase measured in extracts of the tissue even in the absence of added substrate; the activities of pyruvate carboxylase, citrate synthase, glutamate dehydrogenase, acetyl-CoA carboxylase, NADP-malate dehydrogenase and NAD-malate dehydrogenase were not changed by insulin. 4. The effect of insulin on pyruvate dehydrogenase activity was inhibited by adrenaline, adrenocorticotrophic hormone and dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate). The effect of insulin was not reproduced by prostaglandin E(1), which like insulin may lower the tissue concentration of cyclic AMP (adenosine 3':5'-cyclic monophosphate) and inhibit lipolysis. 5. Adipose tissue pyruvate dehydrogenase in extracts of mitochondria is almost totally inactivated by incubation with ATP and can then be reactivated by incubation with 10mm-Mg(2+). In this respect its properties are similar to that of pyruvate dehydrogenase from heart and kidney where evidence has been given that inactivation and activation are catalysed by an ATP-dependent kinase and a Mg(2+)-dependent phosphatase. Evidence is given that insulin may act by increasing the proportion of active (dephosphorylated) pyruvate dehydrogenase. 6. Cyclic AMP could not be shown to influence the activity of pyruvate dehydrogenase in mitochondria under various conditions of incubation. 7. These results are discussed in relation to the control of fatty acid synthesis in adipose tissue and the role of cyclic AMP in mediating the effects of insulin on pyruvate dehydrogenase.
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PMID:Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. 515 98

The contribution of muscle tissue to the increased metabolic efficiency of the obese (fa/fa) Zucker rat at 6 wk of age was examined. In vitro O2 consumption was similar in obese and nonobese soleus and extensor digitorum longus (EDL) muscles, whether the animals were fed ad libitum, fasted, or treated with triiodothyronine. No phenotypic difference in the in vitro O2 consumption was seen when the muscles were preincubated with or without exogenous insulin. Pyruvate kinase, citrate synthase, succinate dehydrogenase, and cytochrome oxidase activities were similar in the soleus and the EDL muscles of both phenotypes. Phosphofructokinase and lactate dehydrogenase activities were higher in the soleus muscles from the obese rats, whereas hexokinase activities were higher in the EDL muscles from the nonobese rats. Mitochondrial and whole muscle homogenate respiration rates were similar in both phenotypes. The soleus and EDL muscles from the obese animals weighed less than those from the nonobese, but empty carcass weights were similar. Taken together these data suggest that muscle mass, muscle O2 consumption, and muscle oxidative capacity are similar in 6-wk-old obese and nonobese rats. Therefore other tissues are probably responsible for the increased metabolic efficiency of the young obese rat.
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PMID:Oxygen consumption and oxidative capacity of muscles from young obese and nonobese Zucker rats. 609 7

Mitochondria and secretory granules were isolated from beta-cell-rich pancreatic islets of ob/ob mice. Crude fractions obtained by differential centrifugation were subjected to centrifugation on isotonic Percoll. The gradient medium was removed from the resulting fractions by gel filtration on Sephacryl S-1000 Superfine. When compared to the crude fractions, the purified mitochondrial fraction exhibited a 4.5-fold increase in citrate synthase activity, a 70% reduction of lysosomal arylsulfatase, and a 40% decrease of contamination with granular insulin. In the purified secretory granule fraction, the insulin content was as high as 60% of the total protein (albumin standard) with arylsulfatase unchanged and no detectable citrate synthase activity.
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PMID:Purification of mitochondria and secretory granules isolated from pancreatic beta cells using Percoll and Sephacryl S-1000 superfine. 635 96

Certain enzymes respond to the binding of substrates and coenzymes by the closure of an active site that lies in a cleft between two domains. We have examined the mechanism of the domain closure in citrate synthase, for which atomic co-ordinates are available for "open" and "closed" forms. We show that the mechanism of domain closure involves small shifts and rotations of packed helices within the two domains and at their interface. Large motions of distant segments of the structure are the cumulative effect of the small relative shifts in intervening pairs of packed segments. These shifts are accommodated not by changes in packing but rather by small conformational changes in side-chains. We call this the helix interface shear mechanism of domain closure. The relative movements of packed helices follow the principles suggested by our recent study of insulin. This mechanism of domain closure is quite different from the hinge mechanisms that allow the rigid body movements of domains in immunoglobulins. The large interface between the domains of citrate synthase precludes a simple hinge mechanism for its conformational change. The helix interface shear mechanism of conformational change occurs in other enzymes that contain extensive domain-domain interfaces.
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PMID:Mechanisms of domain closure in proteins. 637 Dec 49

Peripheral adaptations to 3 months of physical endurance training without food restrictions were studied in skeletal muscles of 14, middle-aged, physically untrained, obese women. In comparison to aged-matched controls of normal weight, the obese group showed significantly lower isometric endurance. In the obese group, physical training resulted in a significant increase of maximal isometric and isokinetic strength. Isokinetic but not isometric endurance also increased after training. The isometric strength of obese women showed a positive correlation with the percentage of FTb fibres. The training (50 min/day, 3 days/w) did not result in any change in body weight, body fat, and the number and weight of fat cells. The 20% increase of VO2 max after training was found to be significantly correlated with the increase in the number of capillaries around muscle fibres. The relative percentage of FTa fibres, the number of capillaries per fibre as well as the activities of citrate synthase, 3-hydroxy-acyl-CoA-dehydrogenase, and hexokinase showed a significant increase after training. The concentrations of glucose during OGTT showed a trend to decrease with a significant decrease at the end glucose curve (120-min value). The concentration of insulin and C peptide and the insulin removal did not change after training. The changes in the concentration of glucose during OGTT was significantly correlated with the increase in muscle capillarization and of dynamic endurance.
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PMID:Physical training in obese women. Effects of muscle morphology, biochemistry and function. 638 Oct 44

The effect of exercise on in vivo insulin sensitivity was examined in lean and obese Zucker rats. Rats (6 to 7 weeks of age) were swum two hours per day or kept sedentary for 8 weeks. Exercise decreased body weight gain as well as percent of fat in both genotypes. Sedentary obese rats had 62% higher gastrocnemius citrate synthase activity per gram of muscle than did lean rats. Exercise increased activity of this oxidative enzyme similarly in both genotypes. Compared to lean rats, obese rats had higher plasma-insulin levels and were less sensitive to insulin during an insulin tolerance test. Although training had no effect on plasma-insulin levels, exercise trained obese rats showed a greater drop in plasma glucose relative to sedentary controls following intravenous injection of three concentrations of insulin. It was concluded that moderate exercise training improved the insulin sensitivity of the obese Zucker rat.
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PMID:Exercise training improves insulin sensitivity in the obese Zucker rat. 639 87

To evaluate the relationships between changes in muscle morphology and metabolic adaptation to physical training in obesity, twenty obese women were subjected to a physical training programme with three sessions a week for 3 months. Physical training resulted in lowering of plasma insulin and improved glucose tolerance. Neither body weight nor body fat changed. With physical training the percentage distribution of fast twitch oxidative (FTa) muscle fibres (m vastus lateralis) increased (from 30.3 +/- 5.1% to 35.2 +/- 4.8%, P less than 0.05) and that of fast twitch glycolytic fibres decreased (from 18.3 +/- 6.6 to 5.8 +/- 4.8%, P less than 0.05). The number of capillaries increased, mainly around slow twitch (ST) fibres (from 4.5 +/- 0.6 to 5.8 +/- 0.8, P less than 0.01) and fast twitch oxidative (FTa) fibres (from 3.9 +/- 0.7 to 4.7 +/- 0.8, P less than 0.01). The activities of oxidative enzymes (cytochrome-c-oxidase and citrate synthase) increased (P less than 0.05) while those of glycolytic enzymes (phosphofructokinase and hexokinase) decreased after physical training (P less than 0.01). Significant negative correlations between plasma insulin and number of capillaries in contact with ST fibres (r = 0.80, P less than 0.001) and FTa fibres (r = 0.62, P less than 0.001) were found before training. The capillary density around those fibres could predict 80% of the explained variance of plasma insulin levels (P less than 0.001). The changes of glucose concentration after training could be predicted by observed changes in enzyme activities. The strong associations between muscle morphology and capillarization and enzyme activities and glucose and insulin concentrations and their changes after training suggest an important regulatory role of muscle which warrants further studies.
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PMID:Relationship between muscle morphology and metabolism in obese women: the effects of long-term physical training. 640 24

Rats were given a daily injection of L-epinephrine, 100 micrograms/100 g body wt, for 6 wk. The hearts of the epinephrine-treated animals were heavier (11.5%), and blood glucose and plasma insulin concentrations were lower than those of control rats. Acute responses to epinephrine were compared in the two groups. An increase in blood glucose and decreases in plasma insulin, liver glycogen, and muscle glycogen occurred in both groups. The magnitude of these responses were similar in the two groups except for the decrease in muscle glycogen, which was smaller in the chronic epinephrine-treatment group. There were no changes in respiratory capacity, citrate synthase or succinate dehydrogenase activities, or in cytochrome c concentration in skeletal muscle in response to 6 wk of epinephrine treatment. These results are compatible with the suggestion that catecholamines may play a role in some of the metabolic and cardiac adaptations to exercise training. However, they argue strongly against the hypothesis that catecholamines are responsible for inducing the increase in muscle mitochondria that occurs in response to exercise training.
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PMID:Adaptive responses of rats to prolonged treatment with epinephrine. 645 52


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