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)

The oxidative capacity of the liver, the heart and skeletal muscles for fatty acids were investigated in preruminant calves fed for 19 d on a milk-replacer containing either coconut oil (CO, rich in 12:0) or tallow (rich in 16:0 and 18:1). Weights of the total body and tissues did not differ significantly between the two groups of animals but plasma glucose and insulin concentrations were lower in the CO group. Feeding on the CO diet induced an 18-fold increase in the hepatic concentration of triacylglycerols. Rates of total and peroxisomal oxidation of [1-14C]laurate, [1-14C]palmitate and [1-14C]oleate were measured in fresh tissue homogenates. Higher rates of total oxidation in liver homogenate and of peroxisomal oxidation in liver, heart and rectus abdominis muscle homogenates were observed with laurate used as substrate. Furthermore, the relative contribution of peroxisomes to total oxidation was 1.9-fold higher in the liver and in the heart with laurate than with oleate or palmitate. Finally, the peroxisomal oxidation rate of oleate was 1.5-fold higher in the hearts of calves fed on the CO diet. Whatever the tissue, citrate synthase (CS, EC 4.1.3.7) and cytochrome c oxidase (COX, EC 1.9.3.1) activities were similar between the two groups of calves but the COX: CS activity ratio was lower in the liver of the CO group. In conclusion, laurate is better catabolized by peroxisomes than long-chain fatty acids, especially in the liver. Elongation of lauric acid after partial oxidation might explain the hepatic triacylglycerol accumulation in calves fed on the CO diet.
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PMID:Effects of dietary coconut oil on fatty acid oxidation capacity of the liver, the heart and skeletal muscles in the preruminant calf. 1065 79

The 26 S proteasome is a large protease complex that catalyzes the degradation of both native and misfolded proteins. These proteins are known to interact with PA700, the regulatory subcomplex of the 26 S proteasome, via a covalently attached polyubiquitin chain. Here we provide evidence for an additional ubiquitin-independent mode of substrate recognition by PA700. PA700 prevents the aggregation of three incompletely folded, nonubiquitinated substrates: the DeltaF-508 mutant form of cystic fibrosis transmembrane regulator, nucleotide binding domain 1, insulin B chain, and citrate synthase. This function does not require ATP hydrolysis. The stoichiometry required for this function, the effect of PA700 on the lag phase of aggregation, and the temporal specificity of PA700 in this process all indicate that PA700 interacts with a subpopulation of non-native conformations that is either particularly aggregation-prone or nucleates misassociation reactions. The inhibition of off-pathway self-association reactions is also reflected in the ability of PA700 to promote refolding of citrate synthase. These results provide evidence that, in addition to binding polyubiquitin chains, PA700 contains a site(s) that recognizes and interacts with misfolded or partially denatured polypeptides. This feature supplies an additional level of substrate specificity to the 26 S proteasome and a means by which substrates are maintained in a soluble state until refolding or degradation is complete.
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PMID:Recognition of misfolding proteins by PA700, the regulatory subcomplex of the 26 S proteasome. 1068 37

The effects of insulin treatment on skeletal muscle characteristics were studied in 18 patients (62 +/- 11 years) with poorly controlled diabetes mellitus type 2 (mean duration 7.5 +/- 6 years). Skeletal muscle biopsy samples were taken from the lateral portion of the quadriceps muscle before and after a period of insulin treatment of 40 +/- 14 days. Enzyme activities (phosphofructokinase, 3-hydroxyacyl-CoA dehydrogenase, citrate synthase, lactate dehydrogenase and creatine kinase) and myoglobin content were assessed. In a subgroup of 11 patients (60 +/- 11 years), skeletal muscle fibre type composition (type I, IIA, IIB and IIC) and fibre type cross-sectional area were also analysed. Following insulin treatment there were 32 and 38% increases, respectively, in the cross-sectional areas of type IIA and IIB fast-twitch fibres (P<0. 02). The fibre type distribution did not change. The myoglobin content in muscle decreased by 20% (P<0.01). Of the enzymes tested, the 3-hydroxyacyl-CoA dehydrogenase activity decreased by 10% (P<0. 04). Serum glucose, HbA1C and serum triglyceride levels decreased (P<0.001) and body weight and arm muscle circumference increased (P<0.02). In conclusion, insulin treatment of patients with poorly controlled non-insulin-dependent diabetes mellitus increased the fast-twitch fibre area, reduced myoglobin levels and decreased muscle enzyme activity related to fatty acid oxidation.
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PMID:Insulin treatment increases skeletal muscle fibre area in patients with diabetes mellitus type 2. 1097 46

The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases even disappearance of fat tissue. Here, we report the effects of leptin (10 and 100 ng.mL-1) on isolated rat adipocytes maintained for 15 h in culture. Leptin decreased the incorporation of acetate into total lipids by 30%. A reduction in this incorporation (42%) was still observed after the leptin-cultivated adipocytes were exposed to a supra-physiological insulin concentration (10 000 microU.mL-1). On the other hand, leptin increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradation by 35 and 50% at concentrations of 10 and 100 ng. mL-1, respectively. Eventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adipocytes. The upregulation of UCP2 mRNA might have contributed to the stimulation of acetate and fatty acid degradation by leptin. The peripheral effects of leptin observed in this study are in line with the general energy dissipating role postulated for this hormone and for UCP2. They suggest mechanisms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system.
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PMID:Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytes. 1099 55

The 90-kDa heat shock protein (Hsp90) is the most abundant molecular chaperone of the eukaryotic cytoplasm. Its cysteine groups participate in the interactions of Hsp90 with the heme-regulated eIF-2alpha kinase and molybdate, a stabilizer of Hsp90-protein complexes. In our present studies we investigated the reactivity of the sulfhydryl groups of Hsp90. Our data indicate that Hsp90 as well as two Hsp90 peptides containing Cys-521 and Cys-589/590 are able to reduce cytochrome c. The effect of Hsp90 can be blocked by sulfhydryl reagents including arsenite and cadmium, which indicates the involvement of the vicinal cysteines Cys589/590 in the reduction of cytochrome c. Hsp90 neither reduces the disulfide bonds of insulin nor possesses a NADPH:quinone oxidoreductase activity. Oxidizing conditions impair the chaperone activity of Hsp90 toward citrate synthase. The high and specific reactivity of Hsp90 cysteine groups toward cytochrome c may indicate a role of this chaperone in modulation of the redox status of the cytosol in resting and apoptotic cells.
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PMID:Reactive cysteines of the 90-kDa heat shock protein, Hsp90. 1114 36

Acute exercise and training increase insulin action in skeletal muscle, but the mechanism responsible for this effect is unknown. Activation of the insulin receptor initiates signaling through both the phosphatidylinositol (PI) 3-kinase and the mitogen-activated protein kinase [MAPK, also referred to as extracellular signal-regulated kinases (ERK1/2)] pathways. Acute exercise has no effect on the PI3-kinase pathway signaling elements but does activate the MAPK pathway, which may play a role in the adaptation of muscle to exercise. It is unknown whether training produces a chronic effect on basal activity or insulin response of the MAPK pathway. The present study was undertaken to determine whether exercise training improves the activity of the MAPK pathway or its response to insulin in obese Zucker rats, a well-characterized model of insulin resistance. To accomplish this, obese Zucker rats were studied by using the hindlimb perfusion method with or without 7 wk of treadmill training. Activation of the MAPK pathway was determined in gastrocnemius muscles exposed in situ to insulin. Compared with lean Zucker rats, untrained obese Zucker rats had reduced basal and insulin-stimulated activities of ERK2 and its downstream target p90 ribosomal S6 kinase (RSK2). Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity. This effect was maintained for at least 96 h in the case of ERK2. The training-induced increase in basal ERK2 activity was correlated with the increase in citrate synthase activity. Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity. The increase in basal ERK2 activity may be related to the response of muscle to training.
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PMID:Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats. 1116 42

The aim of this study was to determine if there is a relationship among skeletal muscle fiber composition, capillarization, blood pressure (BP) and/or the components of the metabolic syndrome. Two groups were compared: 8 recently diagnosed, untreated, hypertensive men (BP > or = 140/90) and 7 normotensive men as controls. Muscle biopsies were taken from the vastus lateralis part of quadriceps femoris muscle in order to assess: fiber type proportion, capillarization, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase activities; lipoprotein lipase mass and activity, free fatty acids and triglycerides. Serum levels of insulin, glucose, cholesterol, uric acid and triglycerides were also assayed. Hypertensive patients had higher insulin levels and insulin resistance [homeostasis model assessment (HOMA)], a decreased hexokinase activity and an increase of muscle lipoprotein lipase mass as compared to controls. Interestingly, correlations among values differ in each group. The percentage of type IIB fibers was related to diastolic BP (blood pressure) in control and to mean BP in hypertensive subjects. Serum cholesterol and glucose were inversely related to the percentage of type I fibers in the control subjects. Negative correlations between capillarization and glucose, cholesterol and uric acid levels were found in control subjects. In all subjects, a strong correlation was found between SBP (systolic BP) and DBP (diastolic BP), and insulin resistance (IR) and uric acid levels. Muscle fiber type proportion and capillarization were related to blood pressure and components of the metabolic syndrome.
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PMID:Muscle fiber composition and capillarization in relation to metabolic alterations in hypertensive men. 1132 89

Congo red (CR) binding, monitored by characteristic yellow-green birefringence under crossed polarization has been used as a diagnostic test for the presence of amyloid in tissue sections for several decades. This assay is also widely used for the characterization of in vitro amyloid fibrils. In order to probe the structural specificity of Congo red binding to amyloid fibrils we have used an induced circular dichroism (CD) assay. Amyloid fibrils from insulin and the variable domain of Ig light chain demonstrate induced CD spectra upon binding to Congo red. Surprisingly, the native conformations of insulin and Ig light chain also induced Congo red circular dichroism, but with different spectral shapes than those from fibrils. In fact, a wide variety of native proteins exhibited induced CR circular dichroism indicating that CR bound to representative proteins from different classes of secondary structure such as alpha (citrate synthase), alpha + beta (lysozyme), beta (concavalin A), and parallel beta-helical proteins (pectate lyase). Partially folded intermediates of apomyoglobin induced different Congo red CD bands than the corresponding native conformation, however, no induced CD bands were observed with unfolded protein. Congo red was also found to induce oligomerization of native proteins, as demonstrated by covalent cross-linking and small angle x-ray scattering. Our data suggest that Congo red is sandwiched between two protein molecules causing protein oligomerization. The fact that Congo red binds to native, partially folded conformations and amyloid fibrils of several proteins shows that it must be used with caution as a diagnostic test for the presence of amyloid fibrils in vitro.
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PMID:Is Congo red an amyloid-specific dye? 1141 Jun 1

Obesity and dysfunctional energy partitioning can lead to the development of insulin resistance and type 2 diabetes. The antidiabetic thiazolidinediones shift the energy balance toward storage, leading to an increase in whole-body adiposity. These studies examine the effects of pioglitazone (Pio) on adipose tissue physiology, accumulation, and distribution in female Zucker (fa/fa) rats. Pio treatment (up to 28 days) decreased the insulin-resistant and hyperlipidemic states and increased food consumption and whole-body adiposity. Magnetic resonance imaging (MRI) analysis and weights of fat pads demonstrated that the increase in adiposity was not only limited to the major fat depots but also to fat deposition throughout the body. Adipocyte sizing profiles, fat pad histology, and DNA content show that Pio treatment increased the number of small adipocytes because of both the appearance of new adipocytes and the shrinkage and/or disappearance of existing mature adipocytes. The remodeling was time dependent, with new small adipocytes appearing in clusters throughout the fat pad, and accompanied by a three- to fourfold increase in citrate synthase and fatty acid synthase activity. The appearance of new fat cells and the increase in fat mass were depot specific, with a rank order of responsiveness of ovarian > retroperitoneal > subcutaneous. This differential depot effect resulted in a redistribution of the fat mass in the abdominal region such that there was an increase in the visceral:subcutaneous ratio, as confirmed by MRI analysis. Although the increased adiposity is paradoxical to an improvement in insulin sensitivity, the quantitative increase of adipose mass should be viewed in context of the qualitative changes in adipose tissue, including the remodeling of adipocytes to a smaller size with higher lipid storage potential. This shift in energy balance is likely to result in lower circulating free fatty acid levels, ultimately improving insulin sensitivity and the metabolic state.
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PMID:Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance. 1147 50

To test the effect of nandrolone on their recovery, six adult half-bred riding horses performed a competition exercise test (CET) and a standardized exercise test (SET) on consecutive days before and after a 2-week treatment with the anabolic steroid nandrolone laurate. Blood samples were collected during and between these tests for the determination of red cell volume and concentrations of blood lactate, plasma glucose, non-esterified fatty acids, glycerol, triglycrides, erythropoietin, cortisol, insulin, and glucagon. Muscle biopsy specimens were taken immediately after the CET and before the SET for analysis of glycogen content, citrate synthase, and 3-hydroxyacyl CoA dehvdrogenase activity. Nandrolone administration increased the rate of muscle glycogen repletion after exercise, an increase that may be explained by increased glucose output by the liver, higher plasma insulin concentration, and increased insulin-independent glucose transport, but not by better availability of lipid fuels during recovery.
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PMID:Effects of nandrolone treatment on recovery in horses after strenuous physical exercise. 1155 92


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