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)

Specific mitochondrial enzyme activities, mitochondrial DNA copy number, and mRNA levels were measured in heart, brain, and liver tissues of a group of alcohol-fed rats and compared with a control group. The results show a significant increase in mitochondrial enzyme activities (citrate synthase, complex IV, complex III, complex I, and complex V), as well as an increase in mitochondrial DNA in the cardiac tissue of the alcohol-fed animals. These data are indicative of an increase in mitochondrial number in the cardiac tissue that may occur as the result of an adaptive response to the alcoholic insult. However, in the liver and brain of the alcohol-treated rat, specific mitochondrial activities were decreased, in particular, complex III and ATP synthase, whereas levels of other mitochondrial enzymes (e.g., citrate synthase, specific mitochondrial transcripts, and mitochondrial DNA levels) do not seem to be affected. These data suggest that a tissue-specific response to alcohol exists that may have a common molecular mechanism in brain and liver, but is different in the heart.
Alcohol Clin Exp Res 1995 Dec
PMID:Heart mitochondria response to alcohol is different than brain and liver. 874 11

A normal mode analysis of the closed form of dimeric citrate synthase has been performed. The largest-amplitude collective motion predicted by this method compares well with the crystallographically observed hinge-bending motion. Such a result supports those obtained previously in the case of hinge-bending motions of smaller systems, such as lysozyme or hexokinase. Taken together, all these results suggest that low-frequency normal modes may become useful for determining a first approximation of the conformational path between the closed and open forms of these proteins.
Proteins 1995 Dec
PMID:Hinge-bending motion in citrate synthase arising from normal mode calculations. 874 51

A total of 300 female broiler chickens were reared from day-old to 10 d of age on the same starter diet. Then they were divided into five groups, receiving a control diet (Group 1) relatively rich in fat (14.3%) and unsaturated fatty acids (87.6%) and standardized with respect to vitamins and minerals, supplemented with 100 mg (Group 2) and 500 mg (Group 4) of RRR-alpha-,gamma-,delta-tocopheryl acetate/kg feed (40.6% alpha-, 41.1% gamma-, 18.3% delta-) or 100 mg (Group 3) and 500 mg (Group 5) all-rac-alpha-tocopheryl acetate/kg feed until slaughter at 6 wk of age. No differences between the supplemented groups were observed with respect to weight gain, feed consumption, packed cell volume (PCV), plasma enzyme activities of creatine kinase (CK) and glutathione peroxidase (GSH-Px), fatty acid composition, and enzyme activities of citrate synthase (CS), and total lactate dehydrogenase (LDH), and 3-OH-acyl-coenzyme A-dehydrogenase (HAD) of breast (Pectoralis major) and thigh (Gastrocnemius interna) muscle. Increasing levels of alpha-, gamma-, and delta-tocopherol were found in blood plasma with increasing dietary levels of these tocopherols. Only alpha-tocopherol was detectable in skeletal muscle and in higher concentrations in thigh than in breast muscle. Hemolysis in vitro and plasma activity of aspartate aminotransferase (ASAT) were lower (P < .01) in Groups 2 and 4 than in Groups 3 and 5. Interactions were observed between dietary type and concentration of tocopherols for plasma CK, GSH-Px, Na+, and K+. No measurable excretion of ethane and pentane was observed in any of the groups. The findings indicate that the oxidative stress in the live animals was minimal. The mixture of natural source RRR-alpha-,gamma-,delta-tocopherols was as efficient in protecting the live chickens as the all-rac-alpha-tocopheryl acetate, when provided on a weight basis as judged from the chosen in vivo parameters of vitamin E status.
Poult Sci 1995 Dec
PMID:Supplementation of broiler diets with all-rac-alpha- or a mixture of natural source RRR-alpha-,gamma-,delta-tocopheryl acetate. 1. effect on vitamin E status of broilers in vivo and at slaughter. 882 89

The rates of increase in O2 uptake (VO2) after step changes in work rate from 25 W to 60% of pretraining peak VO2 (VO2 peak) were measured at various times during an endurance training program (2 h/day at 60% pretraining VO2 peak). Seven untrained males [23 +/- 1 (SE) yr] performed a series of repeated step changes in work rate before training (PRE) and after 4 days (4D), 9 days (9D), and 30 days (30D) of training. VO2 kinetic responses were determined from breath-by-breath data averaged across four repetitions and analyzed using a two-component exponential model. Mean response time (time taken to reach 63% of steady-state VO2) was faster (P < 0.01) than PRE (38.1 +/- 2.6 s) at both 4D (34.9 +/- 2.4 s) and 9D (32.5 +/- 1.8 s) and was faster (P < 0.01) at 30D than at all other times (28.3 +/- 1.0 s). Blood lactate concentrations (after 6 min of cycling) were also lower at 4D and 9D than PRE (P < 0.01) and were lower at 30D than at all other times (P < 0.01). VO2 peak was unchanged from PRE (3.52 +/- 0.20 l/min) at 8D (3.55 +/- 0.20 l/min) but was increased (P < 0.01) at 30D (3.89 +/- 0.18 l/min). Muscle oxidative capacity (maximal citrate synthase activity) was not significantly increased until 30D (P < 0.01). It is concluded that at least part of the acceleration of whole body VO2 kinetics with endurance training is a rapid phenomenon, occurring before changes in VO2 peak and/or muscle oxidative potential.
J Appl Physiol (1985) 1995 Dec
PMID:Progressive effect of endurance training on VO2 kinetics at the onset of submaximal exercise. 884 53

Tissue capillarity and tissue enzyme activity (citrate synthase and lactate dehydrogenase) were determined for two red muscles and two white muscles from the domestic chicken during normal maturation and, for one red muscle, during muscle hypertrophy. Muscle fiber cross sectional area increased with muscle mass during normal maturation and with the additional increase in muscle mass following hypertrophy. Normal maturation and hypertrophy did not affect lactate dehydrogenase activity or citrate synthase activity for the muscles with anaerobic fiber types. Citrate synthase activity per unit muscle mass was positively correlated with muscle capillary density for the muscles with aerobic fiber types. Capillary to fiber ratios increased with fiber size and were significantly higher in muscles with aerobic fibers than in muscles with nonaerobic fibers. However, capillary densities decreased with maturation and with fiber hypertrophy. For each of the muscles sampled, the number of capillaries per unit linear distance of muscle fiber perimeter was independent of muscle fiber growth during normal maturation and during hypertrophy. The results from the present work are consistent with the hypothesis that muscle fiber type and muscle fiber surface area may be the primary determinants of capillary growth during normal maturation and during fiber hypertrophy.
Respir Physiol 1995 Dec
PMID:Capillary growth in chick skeletal muscle with normal maturation and hypertrophy. 890 20

The activities of key enzymes in the valine catabolic pathway--branched-chain aminotransferase, branched-chain alpha-keto acid dehydrogenase complex, methacrylyl (MC)-coenzyme A (CoA) hydratase (crotonase), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolase--were measured in normal and cirrhotic human livers. Unlike rat liver, which does not contain branched-chain aminotransferase, the aminotransferase activity in the normal liver was measurable and is increased somewhat in cirrhosis of the human liver. The total activity of branched-chain alpha-keto acid dehydrogenase complex in the normal human liver was approximately 1% of that in rat liver, and 20% to 30% of the complex was in the active form in both normal and cirrhotic livers. Only the actual activity of the enzyme was significantly decreased by cirrhosis. These results suggest that human liver is less active than rat liver in the catabolism of branched-chain amino and alpha-keto acids. Activities of MC-CoA hydratase and HIB-CoA hydrolase in human liver were very high compared with that of branched-chain alpha-keto acid dehydrogenase complex, suggesting an important role for these enzymes in catabolism of a potentially toxic compound, MC-CoA, formed as an intermediate in the catabolism of valine and isobutyrate. Cirrhosis resulted in a significant decrease in HIB-CoA hydrolase activity but had no effect on the citrate synthase activity, suggesting that the decrease in HIB-CoA hydrolase activity does not reflect a general decrease in mitochondria but that it may contribute to cellular damage that culminates in liver failure.
Hepatology 1996 Dec
PMID:The valine catabolic pathway in human liver: effect of cirrhosis on enzyme activities. 893 68

Protein disulfide-isomerase (PDI) catalyzes the formation and isomerization of disulfides during oxidative protein folding in the eukaryotic endoplasmic reticulum. At high concentrations, it also serves as a chaperone and inhibits aggregation. However, at lower concentrations, PDI can display the unusual ability to facilitate aggregation, termed anti-chaperone activity (Puig, A., and Gilbert, H. F. (1994) J. Biol. Chem. 269, 7764-7771). Under reducing conditions (10 mM dithiothreitol) and at a low concentration (0.1-0. 3 microM) relative to the unfolded protein substrate, PDI facilitates aggregation of alcohol dehydrogenase (11 microM) that has been denatured thermally or chemically. But at higher concentrations (>0.8 microM), PDI inhibits aggregation under the same conditions. With denatured citrate synthase, PDI does not facilitate aggregation, but higher concentrations do inhibit aggregation. Anti-chaperone behavior is associated with the appearance of both PDI and substrate proteins in insoluble complexes, while chaperone behavior results in the formation of large (>500 kDa) but soluble complexes that contain both proteins. Physiological concentrations of calcium and magnesium specifically increase the apparent rate of PDI-dependent aggregation and shift the chaperone activity to higher PDI concentrations. However, calcium has no effect on the Km or Vmax for PDI-catalyzed oxidative folding, suggesting that the interactions that lead to chaperone/anti-chaperone behavior are distinct from those required for catalytic activity. To account for this unusual behavior of a folding catalyst, a model with analogy to classic immunoprecipitation is proposed; multivalent interactions between PDI and a partially aggregated protein stimulate further aggregate formation by noncovalently cross-linking smaller aggregates. However, at high ratios of PDI to substrate, cross-linking may be inhibited by saturation of the sites with PDI. The effects of PDI concentration on substrate aggregation and the modulation of the behavior by physiological levels of calcium may have implications for the involvement of PDI in protein folding, aggregation, and retention in the endoplasmic reticulum.
J Biol Chem 1996 Dec 27
PMID:Facilitated protein aggregation. Effects of calcium on the chaperone and anti-chaperone activity of protein disulfide-isomerase. 896 36

A 30-kD coenzyme A (CoA)-binding protein was isolated from spinach (Spinacea oleracea) chloroplast soluble extracts using affinity chromatography under conditions in which 95% of the total protein was excluded. The 30-kD protein contains an eight-amino-acid sequence, DVRLYYGA, that is identical to a region in a 36-kD protein of unknown function that is encoded by a kiwifruit (Actinidia deliciosa) cDNA. Southern blotting also detected a spinach gene that is related to the kiwifruit cDNA. The kiwifruit 36-kD protein that was synthesized in Escherichia coli was imported into chloroplasts and cleaved to a 30-kD form; it was processed to the same size in an organelle-free assay. Furthermore, the kiwifruit protein specifically bound to CoA. The kiwifruit protein contains a single cysteine within a domain that is related to the peroxisomal beta-ketoacyl-CoA thiolases, which catalyze the CoA-dependent degradative step of fatty acid beta-oxidation. Within 50 amino acids surrounding the cysteine, considered to be part of the thiolase active site, the kiwifruit protein shows approximately 26% sequence identity with the mango, cucumber, and rat peroxisomal thiolases. N-terminal alignment with these enzymes, relative to the cysteine, indicates that the 36-kD protein is cleaved after serine-58 during import, agreeing with the estimated size (approximately 6 kD) of a transit peptide. The 30-kD protein is also related to the E. coli and mitochondrial thiolases, as well as to the acetoacetyl-CoA thiolases of prokaryotes. Features distinguish it from members of the thiolase family, suggesting that it carries out a related but novel function. The protein is more distantly related to chloroplast beta-ketoacyl-acyl carrier protein synthase III, the initial condensing enzyme of fatty acid synthetase that utilizes acetyl-CoA.
Plant Physiol 1996 Dec
PMID:Identification of a chloroplast coenzyme A-binding protein related to the peroxisomal thiolases. 897 3

Cytokines exert autocrine and paracrine effects on the heart, some of which may be mediated by inducible nitric oxide synthase (i-NOS) expression. We studied the effects of cytokine-mediated NO synthesis on cell injury in the presence of deoxyglucose (DOG) and cyanide (CV)(20 mM DOG and 2 mM CN) for up to 3 hours and during recovery (18 hours). The influence of heat shock protein-70 on the extent of myocyte damage was also assessed. IL-1 beta and gamma-IFN act synergistically to enhance NO synthesis by cardiac myocytes. When these cytokines are present, the rate of ATP depletion after DOG and CN is significantly greater than in their absence. When IL-1 beta and gamma-IFN are added with the NOS inhibitor, L-monomethyl-L-arginine (L-NMMA), or when a cytokine that does not produce NO (TNF-alpha) is present, the rate of ATP depletion is no different from the rate seen with DOG and CN alone. After recovery for 18 hours, myocytes that were exposed to IL-1 beta and gamma-IFN release more lactic dehydrogenase and have significantly lower levels of ATP. L-NMMA decreases lactic dehydrogenase release and maintains ATP at levels similar to metabolically inhibited cells in the absence of these cytokines. Consistent with the decreased recovery in ATP with cells incubated with DOG and CN plus IL-1 beta and gamma-IFN is a decrease in cytochrome oxidase activity. Decreases in cellular ATP correspond to increased levels of heat shock protein-70 measured in myocytes after 18 hours of recovery after metabolic inhibition in the presence of IL-1 beta and gamma-IFN. In contrast, prior induction of heat shock protein-70 reduces the rate of ATP depletion in myocytes treated with DOG and CN and maintains ATP at levels that are significantly higher than those seen in non-heat-shocked cells. Recovery of cells exposed to heat shock is also greater, as seen by decreased lactic dehydrogenase and citrate synthase release. The heat-shocked myocytes contain significantly more glycogen than the cells that were not heat shocked. The increased cellular glycogen is likely responsible for the greater lactate production and slower rates of ATP depletion in the heat-shocked, metabolically inhibited cells. Cell survival under conditions of metabolic inhibition is closely related to cellular ATP preservation.
Lab Invest 1996 Dec
PMID:Response of the neonatal rat cardiomyocyte in culture to energy depletion: effects of cytokines, nitric oxide, and heat shock proteins. 897 76

1. To examine metabolic correlates of insulin resistance in skeletal muscle, we used 31P magnetic resonance spectroscopy to study glycogenolytic and oxidative ATP synthesis in leg muscle of lean and obese Zucker rats in vivo during 6 min sciatic nerve stimulation at 2 Hz. 2. The water content of resting muscle was reduced by 21 +/- 7% in obese (insulin-resistant) animals compared with lean animals, whereas the lipid content was increased by 140 +/- 70%. These results suggest that intracellular water content was reduced by 17% in obese animals. 3. During exercise, although twitch tensions were not significantly different in the two groups, rates of total ATP synthesis (expressed per litre of intracellular water) were 48 +/- 20% higher in obese animals, suggesting a 50 +/- 8% reduction in intrinsic "metabolic efficiency'. Changes in phosphocreatine and ADP concentration were significantly greater in obese animals than in lean animals, whereas changes in intracellular pH did not differ. 4. These results imply that oxidative ATP synthesis during exercise is activated earlier in obese animals than in lean animals. This difference was not fully accounted for by the greater increase in the concentration of the mitochondrial activating signal ADP. Neither the post-exercise recovery kinetics of phosphocreatine nor the muscle content of the mitochondrial marker enzyme citrate synthase was significantly different in the two groups. The increased oxidative ATP synthesis in exercise must therefore be due to altered kinetics of mitochondrial activation by signals other than ADP. 5. Thus, the insulin-resistant muscle of obese animals may compensate for its decreased efficiency (and consequent increased need for ATP) by increased reliance on oxidative ATP synthesis.
Clin Sci (Lond) 1996 Dec
PMID:Increased oxidative and delayed glycogenolytic ATP synthesis in exercising skeletal muscle of obese (insulin-resistant) Zucker rats. 897 4


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