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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Merocyanine 540 (MC 540) is a photosensitizing dye that is used clinically for the purging of autologous bone marrow grafts and preclinically for the inactivation of enveloped viruses in blood products. Its mechanism of action is not yet well understood. This paper investigates the sites of MC 540-mediated photodamages in L1210 leukemia cells by examining the effects of MC 540-sensitized photoirradiation on several soluble and membrane-bound marker enzymes. When exposed to MC 540 and white light under a standard set of conditions, the activities of Na+/K(+)-ATPase, Mg2(+)-ATPase, and 5'-nucleotidase (three plasma membrane-bound enzymes) were reduced by 54, 49, and 55%, respectively. None of the intracellular enzymes included in this survey was affected by MC 540-sensitized photoirradiation as long as the plasma membrane remained intact. The two soluble enzymes, lactate dehydrogenase and malate dehydrogenase, remained refractory to MC 540-sensitized photoirradiation even after the plasma membrane had been disrupted. By contrast, the activities of the membrane-bound enzymes, NADPH-cytochrome c reductase and succinate dehydrogenase, were reduced in cell lysates by 55 and 81%, respectively. Purified NADPH-cytochrome c reductase was about 3 times less sensitive than the microsomal enzyme, suggesting that the membrane environment facilitated photoinactivation. The MC 540-sensitized photoinactivation of enzymes was accelerated in the presence of deuterium oxide and inhibited if oxygen in the medium was displaced by nitrogen or azide was added to the medium. Taken together, these data support the view that the plasma membrane is a major target of MC 540-mediated photodamages, that the inactivation of membrane-bound enzymes is an oxidative process, and that at least some photodynamic damages are mediated by type II chemistry.
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PMID:Merocyanine 540-sensitized photoinactivation of soluble and membrane-bound enzymes in L1210 leukemia cells. 217 31

Earlier investigations involving chronic muscle stimulation have shown that skeletal muscle cells possess a much greater metabolic plasticity than had previously been recognized. We have described more fully the time course for the changes in different enzyme systems in single fibres of rabbit fast-twitch tibialis anterior (TA) muscles after periods of continuous stimulation of up to 10 weeks. After 2-5 wk every fibre shows higher levels of many oxidative enzymes than any control fibre; in some cases these levels are 2-10 times higher (well above any found even in the control soleus, a slow-twitch muscle). Citrate synthase, hexokinase and 3-oxoacid CoA-transferase are representatives of this group of enzymes. Other enzymes, such as malate dehydrogenase and amino acid aminotransferases also increase dramatically, but peak single fibre levels do not reach much above the highest in controls. These differential effects confirm at the single fibre level that chronic stimulation can alter mitochondrial composition. According to their staining reaction for myofibrillar ATPase, TA fibres are approximately 25% type IIA, and 75% type IIB, but by 5 wk these are converted to a mixture of type I, IIA and IIC fibres. At 5 wk, levels of glycolytic and high-energy phosphate transfer enzymes had decreased by 80% or more, and seemed to be adjusted to levels appropriate to their (new) ATPase type. This is in contrast to many enzymes of oxidative metabolism, which increase without synchronization with fibre type change. Determinations of metabolite concentrations in individual fibres from muscles freeze-clamped after varying periods of stimulation gave results which differ strikingly from data for acute stimulation. The findings reinforce our previous view that the high levels of ATP utilization engendered by chronic stimulation of muscle elicit a matching response in ATP production through a series of profound adaptations. Some of these are never encountered under the less extreme conditions of endurance exercise. Such features add to the interest and value of the chronic stimulation model as a means of studying the metabolic plasticity of muscle.
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PMID:Chronic stimulation of mammalian muscle: enzyme and metabolic changes in individual fibres. 252 28

Several functional parameters were studied in a non-synaptic population of brain mitochondria from rats made cirrhotic by chronic treatment with carbon tetrachloride, with and without coma produced by a single injection of ammonium acetate. The following changes were observed in mitochondria from cirrhotic rats, independently of the presence of coma: (a) a large decrease in oxygen consumption with pyruvate-malate as substrate, but not with succinate, in both states 3 and 4; (b) a modified volume oscillation pattern, characterized by a notable diminution in the amplitude of the oscillation; (c) an altered pattern of acyl groups, with a decrease in the proportion of unsaturated with respect to saturated fatty acids. The following parameters were also measured in brain mitochondria from the cirrhotic rats and were found unchanged: (a) malate dehydrogenase and ATPase activities; (b) content of cytochromes; (c) phospholipid composition; (d) total fatty acid content. The possible significance of the changes observed is discussed in terms of the membranal and biochemical alterations that may be involved in the mechanism of hepatic encephalopathy.
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PMID:Functional changes of brain mitochondria during experimental hepatic encephalopathy. 253 14

Oral administration of DEHP, 1000 mg/kg body weight, to rats daily from 6 to 15 day of gestation resulted in retardation of fetal growth and increase in fetal liver weight which contained significant quantities of DEHP. The activities of mitochondrial succinate dehydrogenase, malate dehydrogenase, cytochrome c oxidase and adenosine triphosphatase were decreased in fetal liver. The data indicate that exposure of mothers to DEHP during pregnancy could adversely affect the fetal livers by interfering with bioenergetics of the cell.
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PMID:Biochemical alterations in rat fetal liver following in utero exposure to di(2-ethylhexyl)phthalate (DEHP). 263 47

Fibers of the garter snake transversus abdominis muscle fall into three classes according to contraction speed: faster and slower twitch and tonic. To determine the relationship between these physiologically determined classes and established mammalian fiber types, individual fibers were assayed for key enzymes representing the major energy-generating pathways in vertebrate muscle. Five such enzymes were examined: lactate dehydrogenase, malate dehydrogenase, adenylokinase, fumarate hydratase, and beta-hydroxyacyl-CoA dehydrogenase. The muscle contained three principal metabolic fiber types. Fast-contracting twitch fibers had low-oxidative but high-glycolytic capacity and therefore resembled mammalian-type fast-twitch glycolytic (FG) fibers. Slower twitch fibers were high oxidative-high glycolytic, similar to mammalian-type fast-twitch, oxidative, glycolytic (FOG) fibers. Tonic fibers were high oxidative-low glycolytic; this metabolic profile is characteristic of type slow-twitch oxidative (SO) fibers in mammals. Activity of the enzyme adenylokinase, which in mammals correlates with contraction speed and myosin adenosine triphosphatase (ATPase) activity, separated these reptilian fibers into three groups that are similar but not identical to those delineated by oxidative and glycolytic enzymes. Adenylokinase and beta-hydroxyacyl-CoA dehydrogenase showed the widest range of activities in snake muscle and, therefore, the greatest ability to discriminate fiber types.
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PMID:Metabolic fiber types of snake transversus abdominis muscle. 273 94

It has been proposed that cellular ageing may be caused by loss of mitochondrial function due to the action of free radicals. To investigate this hypothesis, antigenic structures of the mitochondrial inner membrane/matrix and of the outer mitochondrial membrane of human diploid fibroblasts were monitored by immunoblotting at four stages during cellular lifespan in vitro. At the same time, specific activities of the enzymes oligomycin-sensitive ATPase (O-S ATPase), malate dehydrogenase (MDH) and glutamate dehydrogenase (GDH) were assayed to assess the functional capacity of cellular oxidative phosphorylation and of the tricarboxylic acid cycle. No changes were found with ageing in inner mitochondrial membrane-associated matrix components, or in the activities of O-S ATPase and MDH. However GDH activity increased significantly with ageing in vitro, possibly indicating greater amino acid utilization for energy production in older cells. There was loss of an outer mitochondrial membrane antigen, of approximate molecular weight 60 kilodaltons (kDa), in the oldest cells tested, which may influence outer membrane transport capacity late in the cellular lifespan. Overall, the results fail to provide support for the hypothesis that ageing primarily results from free radical-induced impairment of mitochondrial function.
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PMID:Mitochondrial antigenic structure and enzyme activity in ageing human diploid fibroblasts. 278 45

Cell-free extracts of two strictly anaerobic mollicutes, Anaeroplasma intermedium 5LA and Asteroleplasma anaerobium 161T, were tested for enzymic activities of intracellular carbohydrate metabolism. Asteroleplasma anaerobium was also tested for enzymes of purine and pyrimidine metabolism. Both organisms had enzymic activities associated with the nonoxidative portion of the pentose phosphate pathway, and with the Embden-Meyerhoff-Parnas pathway. The 6-phosphofructokinase (PFK) of Asteroleplasma anaerobium was ATP-dependent, whereas the PFK of Anaeroplasma intermedium was PPi-dependent. The two anaerobic mollicutes also differed with respect to the enzymes that converted phosphoenolpyruvate (PEP) to pyruvate; Anaeroplasma intermedium had pyruvate kinase activity, but Asteroleplasma anaerobium had pyruvate, orthophosphate dikinase activity (PPi-dependent). Both organisms had lactate dehydrogenase activity which was activated by fructose 1,6-bisphosphate (Fru-1,6-P2). Anaeroplasma intermedium had activity for PEP carboxykinase (activated by Fru-1,6-P2), but Asteroleplasma anaerobium did not. PEP carboxytransphosphorylase activity was not detected in either organism. Anaeroplasma intermedium had malate dehydrogenase and isocitrate dehydrogenase activities, but it had no activities for the three other tricarboxylic acid cycle enzymes examined; Asteroleplasma anaerobium had malate dehydrogenase activity only. Asteroleplasma anaerobium had enzymic activities for the interconversion of purine nucleobases, (deoxy)ribonucleosides, and (deoxy)ribomononucleotides, including PPi-dependent nucleoside kinase, reported heretofore only in some other mollicutes. Asteroleplasma anaerobium could synthesize dTDP by the thymine salvage pathway if deoxyribose 1-phosphate was provided, and it had dUTPase, ATPase, and dCMP kinase activities. It lacked (deoxy)cytidine deaminase, dCMP deaminase, and deoxycytidine kinase activities.
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PMID:Enzymic activities of carbohydrate, purine, and pyrimidine metabolism in the Anaeroplasmataceae (class Mollicutes). 281 26

The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 micrograms/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.
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PMID:Picket-fence porphyrins as potential phototherapeutic agents. 283 16

Single fibers of rabbit fast-twitch tibialis anterior (TA) muscles were analyzed after continuous low-frequency stimulation for up to 8 wk. After 2-5 wk, every fiber showed higher levels of citrate synthase, hexokinase, and 3-oxoacid CoA-transferase than any control fiber; in some cases these levels were 2-10 times higher (well above any found even in the control soleus, a slow-twitch muscle). Average levels of malate dehydrogenase and alanine transaminase also rose dramatically, but peak single fiber levels were not much above the highest in controls. These differential effects confirm at the single fiber level that chronic stimulation can alter mitochondrial composition. Lactate dehydrogenase, fructose-bisphosphatase, and adenylate kinase declined to levels far below those of any control TA fiber, and, in the case of fructose-bisphosphatase, to within the activity range of control soleus fibers. According to their staining reaction for myofibrillar ATPase, TA fibers were initially 23% type IIA, and 74% type IIB, but by 5 wk these had been converted to a mixture of type I, IIA, and IIC fibers. At 5 wk, levels of lactate dehydrogenase, adenylate kinase, and malate dehydrogenase were characteristic of their (new) ATPase type, but 3-oxoacid CoA transferase had increased to levels 6-15 times higher than in control fibers of the same type.
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PMID:Chronic stimulation of mammalian muscle: enzyme changes in individual fibers. 302 Sep 91

Experimental hyperthyroidism induced in rats by daily injections of 3,3',5,5'-tetraiode-L-thyroxine (0.5 mg/kg i.p.) for 14 days resulted in a significant increase in heart weight and heart weight/body weight ratio. Hemodynamic and morphological studies were performed in one group. Thyroxine-treated rats showed a characteristic cardiovascular hyperdynamic state, such as tachycardia and augmented rate of contraction, but no evidence of heart failure such as elevated end-diastolic pressures. The cardiac cells in hyperthyroid rats had a significantly larger diameter and more mitochondria than did those of the control rats. In another group the activities of cardiac enzymes involved in energy utilization and liberation were measured biochemically and compared with those of normal controls. Hyperthyroidism resulted in increased specific activity of cytochrome C oxidase and actomyosin ATPase in the myocardium. The specific activity of long-chain acyl-CoA synthetase, carnitine palmityl-transferase, carnitine acetyltransferase, malate dehydrogenase and citrate synthase showed a moderate to marked increment, whereas the specific activity of lactate dehydrogenase and pyruvate kinase remained at the control values. These results suggest that in hyperthyroid rat hearts the functions of both energy liberation and utilization systems are enhanced to meet the added workload. Moreover, the increased activity of the enzymes participating in fatty acid metabolism suggest that in thyroxine-induced hypertrophic and hyperdynamic rat hearts, fatty acids contribute more to the energy supply than do carbohydrates.
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PMID:Biochemical and morphological study of cardiac hypertrophy. Effects of thyroxine on enzyme activities in the rat myocardium. 315 81


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