Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: T03G11 .9
 340,653 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of various mitochondrial coenzymes and metabolities on the activities of 3-oxoacyl-CoA thiolase (EC 2.3.1.16) and acetoacetyl-CoA thiolase (EC 2.3.1.9) from pig heart were investigated with the aim of elucidating the possible regulation of these two enzymes. Of the compounds tested, acetyl-CoA was the most effective inhibitor of both thiolases. However, 3-oxoacyl-CoA thiolase was more severly inhibited by acetyl-CoA than was acetoacetyl-CoA thiolase. 3-Oxoacyl-CoA thiolase was also significantly inhibited by decanoyl-CoA while acetoacetyl-CoA thiolase was inhibited by 3-hydroxybutyryl-CoA as strongly as it was by acetyl-CoA. All other compounds either did not affect the thiolase activities or only at unphysiologically high concentrations. The inhibition of acetoacetyl-CoA thiolase by acetyl-CoA was linear and apparently noncompetitive with respect to CoASH (Ki = 125 microM) whereas that of 3-oxoacyl-CoA thiolase was nonlinear. However at low concentrations of acetyl-CoA the inhibition of 3-oxoacyl-CoA thiolase was linear competitive with respect to CoASH (Ki = 3.9 microM). It is concluded that 3-oxoacyl-CoA thiolase, but not acetoacetyl-CoA thiolase, will be completely inhibited by acetyl-CoA at concentrations of CoASH and acetyl-CoA which are assumed to exist intramitochondrially at state-4 respiration. It is suggested that fatty acid oxidation in heart muscle at sufficiently high concentrations of plasma free fatty acids is controlled via the regulation of 3-oxoacyl-CoA thiolase by the acetyl-CoA/CoASH ratio which is determined by the rate of the citric acid cycle and consequently by the energy demand of the tissue.
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PMID:Regulation of thiolases from pig heart. Control of fatty acid oxidation in heart. 610 61

To understand the mechanism underlying bronchial hyperreactivity in the Basenji-Greyhound (BG) dog, the effects of propranolol (2 mg/kg) and hexamethonium (5 mg/kg) on base-line pulmonary mechanics and on the bronchial response to aerosol challenges of citric acid and methacholine were studied in five BG dogs. Both propranolol and hexamethonium increased base-line pulmonary resistance (RL) from 0.69 +/- 0.05 (means +/- SE) cmH2O.l-1.s to 1.67 +/- 0.10 (P less than 0.05) and 2.22 +/- 0.45 cmH2O.1-1.s (P less than 0.05) and decreased dynamic compliance (Cdyn) from 190 +/- 10 ml/cmH2O to 154 +/- 9 (P less than 0.05) and 140 +/- 9 (P less than 0.05) ml/cmH2O, respectively. Both propranolol and hexamethonium potentiated the pulmonary response to 10% citric acid given for 5 min (P less than 0.05). RL postchallenge was 4.4 +/- 0.23, 8.1 +/- 0.81, and 7.8 +/- 0.31 cmH2O.l-1.s, and Cdyn was 78 +/- 5, 58 +/- 6, and 51 +/- 3 ml/cmH2O in untreated, propranolol-pretreated, and hexamethonium-pretreated animals. In untreated BG dogs, methacholine (0.075 mg/ml) increased RL from 0.94 +/- 0.25 to 2.2 +/- 0.21 cmH2O.l-1.s (234%) and decreased Cdyn from 223 +/- 39 to 141 +/- 14 ml/cmH2O (63%). In the same animals pretreated with propranolol, methacholine (0.075 mg/ml) increased RL from 1.9 +/- 0.66 to 4.8 +/- 1.37 cmH2O.l-1.s (253%) and decreased Cdyn from 144 +/- 35 to 81 +/- 15 ml/cmH2O (56%). We conclude that propranolol produces airway constriction in BG dogs, as in asthmatic humans and that the effects of propranolol on airways in BG dogs are not due to parasympathetic or alpha-adrenergic predominance.
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PMID:Basenji-greyhound dog model of asthma: pulmonary responses after beta-adrenergic blockade. 611 1

To investigate sex differences in the organization of enzyme activities of energy supplying metabolism in skeletal muscle, samples of the vastus lateralis were extracted from active but untrained males (n = 16) and females (n = 17), ranging in age from 18 to 22 years. Muscle tissue from 2 different biopsy samples from each subject were analyzed for enzymes representative of the citric acid cycle (succinic dehydrogenase, SDH), beta-oxidation of fatty acids (3-hydroxyacyl CoA dehydrogenase, HAD), glycogenolysis (phosphorylase, PHOSPH), glycolysis (pyruvate kinase, PK; phosphofructokinase, PFK and lactate dehydrogenase, LDH) and glucose phosphorylation (hexokinase, HK). The results indicated that the maximal activities of PFK, PK, LDH and PHOSPH, HK and SDH averaged between 15 and 32% higher in the males than in the females. No significant differences between the sexes were found for HAD. When enzyme activity ratios were calculated, sex differences were only evident for the HAD/SDH ratio (mean +/- SD; females = 0.56 +/- 0.20; males = 0.41 +/- 0.11 and for the PFK/HAD ratio (females = 7.40 +/- 1.6; males = 9.58 +/- 1.9). The findings suggest that (1) the females have a significantly lower overall capacity for aerobic oxidation and for anaerobic glycolysis than the males; (2) the females have a greater capacity for beta-oxidation relative to the capacity of the citric acid cycle; and (3) the glycolytic potential relative to the potential for beta-oxidation is lower in the females.
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PMID:Male and female differences in enzyme activities of energy metabolism in vastus lateralis muscle. 623 35

The effect of pretreatment with prostaglandin F2 alpha (PGF2 alpha) on the bronchial sensitivity to histamine and methacholine has been studied in three groups of six normal subjects, and compared with the effect of citric acid aerosol as a non-specific stimulant of bronchial irritant receptors. Aerosols were generated by Wright's nebulizer and dose-response curves to histamine and methacholine constructed following preadministration of saline, prostaglandin F2 alpha or citric acid. Following prostaglandin F2 alpha pretreatment, the PC20 histamine fell from 12.9 mg/ml to 3.4 mg/ml (P less than 0.01), but the PC20 methacholine was unchanged. Citric acid was without effect. The results indicate that prostaglandin F2 alpha can increase bronchial sensitivity to inhaled histamine, possibly via a direct effect on the airway smooth muscle.
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PMID:The influence of pretreatment with prostaglandin F2 alpha on bronchial sensitivity to inhaled histamine and methacholine in normal subjects. 637 47

A method was developed for the determination of aflatoxin B1 in commercially prepared feeds. The method incorporates methylene chloride and citric acid solution extraction, cleanup on a small silica gel column, and thin layer chromatography for quantitation. Commercial turkey starter, catfish chow, medicated pig starter, broiler finisher, rabbit chow, horse feed, rat chow, and dog chow were investigated. The feeds were spiked with naturally contaminated corn at 4 different levels of aflatoxin B1 (16-130 microgram/kg). Three assays were run on each of the 32 combinations of feed and levels of aflatoxin. Mean recoveries were 85.9-92.8% at levels of 16.5, 32.9, 65.8, and 131.6 micrograms/kg. The relative standard deviation per assay was 18.6%. This method is more rapid and less involved than most previously published methods for mixed feeds.
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PMID:Extraction and thin layer chromatography of aflatoxin B1 in mixed feeds. 640 52

Male Sprague-Dawley rats were treated daily by gastric intubation (6 days/wk) with 100 mg aluminium/kg body weight in the form of aluminium hydroxide (9 wk) or aluminium citrate (4 wk), with citric acid (4 wk) or with tap-water (control, 9 wk). Young adult and aged Wistar rats were treated with 100 mg aluminium/kg body weight as aluminium hydroxide or with carboxymethylcellulose (vehicle controls). The cerebral cortex, hippocampus, cerebellum and samples of bone from each rat were analysed for aluminium, after digestion with nitric acid, using graphite furnace atomic absorption spectroscopy. The mean aluminium concentrations detected in the control Sprague-Dawley rats were 0.013-0.022 microgram/g wet weight in the various brain regions and 0.355 microgram/g in the bone. No significant increase in tissue aluminium concentrations was observed in Sprague-Dawley or Wistar rats after treatment with aluminium hydroxide. However the rats treated with aluminium citrate showed significantly increased concentrations of aluminium in all the brain regions studied (0.057-0.121 microgram A1/g) and in the bone (12.9 micrograms A1/g). Elevated aluminium concentrations in the cerebral cortex and bone were also observed in the animals fed citric acid suggesting possible absorption of the citrate chelate presumably formed with the traces of aluminium present in the diet.
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PMID:Aluminium concentrations in the brain and bone of rats fed citric acid, aluminium citrate or aluminium hydroxide. 653 88

Serum concentrations of chlortetracycline (CTC) in healthy chickens were determined for the 24-hour period after they were given CTC (with and without citric acid) as an oral (25 mg/kg) or IV (0.9 mg/kg) dose. The oral time-course drug data were fitted adequately by a 2-compartment pharmacokinetic model with absorption. The resulting absorption rate constant (Ka) for the birds orally given CTC with citric acid was nearly equal to that for the birds given CTC alone. Although the uptake of orally administered CTC was rapid, only a small fraction of the dose was absorbed. The administration of citric acid-CTC significantly increased the mean serum concentration of CTC and the fraction of the dose absorbed. The citric acid-CTC mixture also produced significantly higher elimination (Kel) and distribution (K12) rate constants for CTC.
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PMID:Pharmacokinetics of chlortetracycline potentiation with citric acid in the chicken. 662 25

Rat hearts have been perfused in vitro with 5 mM glucose and either 5 mM acetate or 1 mM pyruvate to achieve steady state conditions, followed by replacement of the acetate with 90% enriched [2-13C]acetate or pyruvate with 90% enriched [3-13C]pyruvate. The hearts were frozen different times after addition of 13C-substrate and neutralized perchloric acid extracts from three pooled hearts per time point were used to obtain high resolution proton-decoupled 13C NMR spectra at 90.55 MHz. The 13C fractional enrichment of individual carbons of different metabolites was calculated from the area of the resolved resonances after correction for nuclear Overhauser enhancement and saturation effects. A mathematical flux model of the citric acid cycle and ancillary transamination reactions was constructed with the FACSIMILE program, and used to solve unknown flux parameters with constant pool sizes by nonlinear least squares analysis of the approximately 200 simultaneous differential equations required to describe the reactions. With [2-13C] acetate as substrate, resonances and line splittings due to 13C-13C spin coupling of the C-2, C-3, and C-4 carbons of glutamate were well resolved. The half-times to reach maximum 13C enrichment were 2.6 min for glutamate C-4 and 8 min for glutamate C-2 and C-3. From these data, a well determined citric acid cycle flux of 8.3 mumol/g dry weight X min was calculated for an observed oxygen consumption of 31 mumol/g dry weight X min. With [3-13C]pyruvate as substrate, resonances of aspartate C-2 and C-3 and of alanine C-3 were well resolved in addition to those of glutamate C-2, C-3, and C-4. Nonlinear least squares fitting of these data to the model gave nonrandomly distributed residuals for the 13C fractional enrichments of glutamate C-4, suggesting an incomplete model, but a well determined cycle flux of 11.9 mumol/g dry weight X min for an oxygen uptake of 35 mumol/g dry weight X min. Our studies demonstrate the practicality of 13C NMR, used in conjunction with mathematical modeling, for the measurement of metabolic flux parameters in living systems.
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PMID:Mathematical analysis of isotope labeling in the citric acid cycle with applications to 13C NMR studies in perfused rat hearts. 664 54

In the present study we used a model of underperfusion or anoxia followed by reperfusion to assess the role of glycolysis by substituting pyruvate or mannitol for glucose as substrate. Hearts were removed from male Sprague-Dawley rats (250-400 g) and perfused by the technique of Langendorff. The perfusate was Krebs-Henseleit bicarbonate buffer gassed with 95% O2, 5% CO2 or with 95% N2, 5% CO2 mixture and containing substrates as can be seen in the figures. The mild ischemia was obtained by reducing the perfusion pressure by 70%, from 60-70 cm H2O to 10-20 cm H2O. The coronary flow was rapidly reduced to 0.8 +/- 0.03 ml/min within the first 5 minutes. After mild ischemia anaerobic glycolysis was accelerated because lactate production in ischemic hearts perfused with glucose (36.2 +/- 15.3 microM/g/min-1) was higher than in the ischemic hearts perfused with mannitol (6.8 +/- 1.9 microM/g/min-1). During mild ischemia or anoxia there was little difference in the rate of release of creatin-kinase for all the substrates tested, but major differences become apparent on reperfusion. In that period the highest values of CK release were found in mannitol perfused hearts, the lowest in glucose perfused hearts. These results suggest that the rate of glycolytic flux during mild ischemia or anoxia may prevent enzyme release. The beneficial effect of glucose has been observed also during reperfusion. In fact enzyme release was higher in hearts reperfused with glucose than with pyruvate. When pyruvate is the only exogenous substrate available for isolated oxigenated hearts, tissue levels of citric acid cycle intermediates are high and oxidation of these substrates can account for 100% of the oxygen consumption. Therefore we suppose that oxidation of noncarbohydrate substrates such as pyruvate in reperfusion is complicated by the high mitochondrial damage. As a consequence anaerobic glycolytic pathway may play a special role in the maintenance of the membrane integrity also in the early phases of reperfusion.
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PMID:[The protective effects of glucose in ischaemia, anoxia and reoxygenation (author's transl)]. 678 66

The effects of airway anesthesia on the magnitude estimation of added inspiratory loads were studied in 5 healthy normal subjects. The subjects assessed the magnitude of a given load by means of a handgrip dynamometer; 5 suprathreshold resistive loads. (range, 2.9 to 21.0 cmH2O/L/s) and 7 suprathreshold elastic loads (range, 4.6 to 24.0 cmH2O/L) were used. Anesthesia of the upper and lower airways was obtained by gargling and inhalation of 4% lidocaine solution; the adequacy of airway anesthesia was assessed by the inhalation of 20% citric acid solution. Studies were performed in the control state and during the airway anesthetized state. The relationship between log added load and log handgrip response, represented by the regression coefficient between these two variables, was in accord with the psychophysical power law of Stevens in all the studies. The regression coefficient during the control state of resistive loads (mean = 0.566) and elastic loads (mean = 0.516) did not alter significantly (p greater than 0.05) during the airway anesthetized state. These results indicate that the magnitude estimation of added inspiratory loads is not primarily mediated through receptors in the upper or lower airways.
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PMID:The effects of airway anesthesia on magnitude estimation of added inspiratory resistive and elastic loads. 684 43


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