Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is widely accepted that a structural organisation favouring interaction between functionally-related enzymes is required for the economy and efficiency of metabolic reactions. Many functionally-related enzymes have been shown to be reversibly bound to cellular structures and to other enzymes at the sites where they are required. Resulting from this binding, close structural proximity and concentration of enzymes, a microenvironment is generated where the product of one enzyme is the substrate of the other. This reduces the diffusion distance for the substrate, saturates binding sites with maximal speed and, as a final outcome, increases the efficiency and economy of function behind these metabolic reactions. Available data indicate that the above-described association between adenosine triphosphatase (ATPase) and enzymes regenerating ATP has an important role in the regulation of ATPase function. A general consensus exists among published studies that the concentration of ATP ([ATP]) is not significantly decreased in fatigued muscle, even in those with severely diminished power output. However, in studies with isolated perfused hearts it has been possible to significantly reduce [ATP] in muscle cells without compromising mechanical activity. An explanation for this discrepancy is connected with local ATP regeneration in the vicinity of ATPase. Furthermore, when ATP regeneration is unable to balance ATP consumption a critical drop in the free energy of ATP hydrolysis is avoided by down-regulation of ATP consumption. The main function of local ATP regeneration is to maintain a low concentration of adenosine diphosphate ([ADP]), and the ADP/ATP ratio in the vicinity of the ATP-binding site of ATPase that is a prerequisite for high thermodynamic efficiency of ATP hydrolysis. Close proximity of creatine kinase and glycolytic enzymes to ATPase and high-affinity binding of substrates generate an ATPase microenvironment, where ADP and ATP are not in free equilibrium with those adenine nucleotides in the surrounding medium. In the physiological range of operation for important cellular ATPases (free energy change of 55 to 60 kJ/mol ATP) only a small fraction of energy, available in ATP, can be utilised, provided that no ATP regeneration takes place. However, ATP regeneration allows utilisation of most of the regenerating capacity, before ATP hydrolysis drops below the critical 55 kJ/mol. The importance of local ATP regeneration increases in parallel with an increase in the rate of ATPase turnover.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Factors limiting adenosine triphosphatase function during high intensity exercise. Thermodynamic and regulatory considerations. 858 47

Limitations in energy supply is a classical hypothesis of muscle fatigue. The present paper reviews the evidence available from human studies that energy deficiency is an important factor in fatigue. The maximal rate of energy expenditure determined in skinned fibres is close to the rate of adenosine triphosphate (ATP) utilisation observed in vivo and data suggest that performance during short bursts of exercise (<5 s duration) primarily is limited by other factors than energy supply (e.g. Vmax of myosine adenosine triphosphatase (ATPase), motor unit recruitment, engaged muscle mass). Within 10 s of exercise maximal power output decreases considerably and coincides with depletion of phosphocreatine. During recovery, maximal force and power output is restored with a similar time course as the resynthesis of phosphocreatine. Increases in muscle store of phosphocreatine through dietary supplementation with creatine increases performance during high-intensity exercise. These findings support the hypothesis that energy supply limits performance during high-intensity exercise. It is well documented that pre-exercise muscle glycogen content is related to performance during moderate intensity exercise. Recent data indicates that the interfibre variation in phosphocreatine is large after prolonged exercise to fatigue and that some fibres are depleted to the same extent as after high-intensity exercise. Despite relatively small decreases in ATP, the products of ATP hydrolysis (Pi and free ADP) may increase considerably. Free ADP calculated from the creatine kinase reaction increases 10-fold both after high-intensity exercise and after prolonged exercise to fatigue. It is suggested that local increases in ADP may reach inhibitory levels for the contraction process.
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PMID:Energy supply and muscle fatigue in humans. 957 71

bis-cyclopentadienyl [Cp] complexes of vanadium(IV) or vanadocenes are rapid and potent inhibitors of human sperm motility with potential as a new class of contraceptive agents. We investigated the utility of boar sperm as a model system to study the mechanisms of drug action because boar sperm lacks phosphocreatine and creatine kinase activity, the essential components of the "phosphagen shuttle" system for human sperm motility. Two representative vanadocenes, vanadocene dichloride [VDC] and bis[pentamethylcyclopentadienyl] vanadium dichloride [VPMDC], in which the bis-Cp rings were substituted with five electron-donating methyl groups were evaluated. The concentration-dependent effects of VDC and VPMDC on spermicidal activity, axonemal dynein adenosine triphosphatase (ATPase) activity, and tyrosine phosphorylation of global sperm proteins were assessed by computer-assisted sperm analysis, spectrophotometry, and immunoblotting, respectively. Both the unsubstituted and the pentamethyl-substituted vanadocene induced rapid sperm immobilization (T(1/2) < 15 s). Substitution of the bis-Cp rings by five methyl groups augmented the SIA of VDC threefold. The EC(50) values for VDC and VPMDC were 2.1 and 0.76 microM, respectively. Spermicidal activity of vanadocenes was not associated with the inhibition of dynein ATPase(s) or increase in tyrosine phosphorylation of sperm proteins. These results suggest that the potent spermicidal activity of vanadocenes against boar sperm is mediated by a unique mechanism that is independent of dynein ATPase activity, phosphatase activity, and phosphocreatine/creatine kinase system. Therefore, boar sperm is a suitable model for further investigating the molecular mechanism of spermicidal action of vanadocenes.
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PMID:Evaluation of boar sperm as a model system to study the mechanism of spermicidal activity of vanadocenes. 1077 10

A 22-year-old man developed unconsciousness, severe quadriplegia and muscle atrophy, and had markedly elevated serum creatine kinase levels after using the high-dose steroid and nondepolarizing neuromuscular blocking agents during the course of sepsis and DIC. On neurological examination, he was lethargic. The patient had generalized muscle weakness and wasting, and diminished deep tendon reflexes. He weakly responsed to painful stimuli on the legs. The motor nerve conduction study demonstrated decreased CMAP (compound muscle action potential) amplitudes. Motor and sensory nerve conduction velocities and their distal latencies were normal. Muscle biopsy revealed marked muscle fiber atrophy predominantly in type 2 fibers and numerous basophilic and a few necrotic fibers. Some atrophic fibers had decreased to absent myosin adenosine triphosphatase activity in their center. Accordingly, he was diagnosed as having acute quadriplegic myopathy (AQM), which has been reported mainly in Western countries. The mechanism of muscle fiber degradation in this myopathy is still unknown. On immunohistochemical analysis to our patient, enzyme activities of various proteases such as calpain, cathepsin B, and proteasomes were increased in the sarcoplasm, especially in the atrophic fibers. We suggest that lysosomal cathepsin, nonlysosomal calpain, and ATP-ubiquitin-proteasome proteolytic pathways participate in muscle fiber degradation in AQM.
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PMID:[A case of acute quadriplegic myopathy]. 1108 98

Thyroid hormone exerts its biological effect by binding to a TR. Both liganded and unliganded TRs regulate the transcription of T(3)-responsive genes. Cofactors with activating or repressing function modulate the transcriptional regulation by TRs. We showed that steroid receptor coactivator 1 (SRC-1)-deficient mice (SRC-1(-/-)) exhibit partial resistance to thyroid hormone at the level of the pituitary thyrotrophs. To determine whether SRC-1 deficiency affects globally T(3)-dependent transcriptional regulation, we studied the effects of thyroid hormone deprivation and replacement on the expression of several genes in different tissues of SRC-1(-/-) and wild-type mice (SRC-1(+/+)). Thyroid hormone deficiency was induced by a low iodine diet (LoI) supplemented with propylthiouracil (PTU) for 2 wk. L-T(3) was injected ip for the last 4 d in one group (PTU+T(3) group), and another group (PTU group) received only vehicle. Levels of mRNAs for T(3)-responsive genes were determined by Northern blotting: GH and TSH beta in pituitary; type 1 iodothyronine 5'-deiodinase, spot 14 (S14), and malic enzyme in liver; and sarcoplasmic reticulum calcium adenosine triphosphatase 2 and myosin heavy chain alpha and beta in heart. Serum parameters, TSH, total cholesterol, creatine kinase, and alkaline phosphatase (AP), were also measured. Hypothyroidism produced a comparable increase in TSH beta mRNA in both genotypes, but its suppression by L-T(3) was attenuated in SRC-1(-/-) mice. In contrast, hypothyroidism failed to reduce S14 mRNA levels in SRC-1(-/-) mice. As a consequence, the response to L-T(3) was not observed in these mice. SRC-1 deficiency had no effect on the expression of the rest of the T(3)-responsive genes examined. Of the four serum parameters, the T(3)-mediated decrease in TSH and changes in AP were attenuated in SRC-1(-/-) mice. We conclude that SRC-1 deficiency altered the expression of only some of the T(3)-responsive genes. SRC-1 appears to be involved not only in transcriptional activation by liganded TRs, but also in the suppression by liganded or unliganded TRs. Some of the effects of SRC-1 may be TR isoform specific.
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PMID:Steroid receptor coactivator-1 deficiency causes variable alterations in the modulation of T(3)-regulated transcription of genes in vivo. 1189 91

We have evaluated the preventive effects of an aqueous Aegle marmelos leaf extract (AMLEt) in isoprenaline (isoproterenol)-induced myocardial infarction in rats. Rats were pretreated with AMLEt (50, 100 or 200 mg kg(-1)) for 35 days. After the treatment period, isoprenaline (200 mg kg(-1)) was administered subcutaneously to rats at an interval of 24 h for two days. The activity of creatine kinase (CK) and lactate dehydrogenase (LDH) was significantly increased in serum and significantly decreased in heart of isoprenaline-treated rats. Pretreatment with AMLEt decreased the activity of CK and LDH in serum and increased them in the heart. The activity of sodium-potassium dependent adenosine triphosphatase (Na(+)K(+)ATPase) was significantly decreased while the activity of calcium dependent adenosine triphosphatase (Ca(2+)ATPase) was simultaneously increased in the heart and aorta. AMLEt pretreatment increased the activity of Na(+)K(+) ATPase and decreased the activity of Ca(2+)ATPase in the heart and aorta simultaneously. The levels of cholesterol and triglycerides increased, while the levels of phospholipids decreased in the heart and aorta of isoprenaline-treated rats. In AMLEt-pretreated rats the levels of cholesterol and triglycerides decreased whereas phospholipids increased in heart and aorta. All the deranged biochemical parameters were restored with 200 mg kg(-1) AMLEt. Similarly alpha-tocopherol (60 mg kg(-1))-pretreatment to isoprenaline-treated rats exhibited a significant effect on all the parameters studied. The results from this study may have clinical relevance.
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PMID:Preventive effect of Aegle marmelos leaf extract on isoprenaline-induced myocardial infarction in rats: biochemical evidence. 1625 65

This study was aimed to evaluate the preventive role of S-allylcysteine (SAC) on creatine kinase-MB, iron, iron binding capacity, uric acid, total protein, membrane-bound enzymes such as sodium potassium-dependent adenosine triphosphatase, calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase, and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol-induced myocardial infarction in rats. Male albino Wistar rats were pre-treated with SAC (50, 100 and 150 mg/kg) daily for a period of 45 days. After the treatment period, isoproterenol (150 mg/kg) was subcutaneously injected in rats at an interval of 24 hr for 2 days. Isoproterenol-induced rats showed significantly (P < 0.05) increased activities of serum creatine kinase-MB and calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase in the heart, and the levels of iron and uric acid in serum and significantly (P < 0.05) decreased the levels of plasma iron binding capacity, plasma total protein, plasma albumin/globulin ratio and activity of sodium potassium-dependent adenosine triphosphatase in the heart. Isoproterenol induction also showed a significant increase in the levels of glycoproteins in serum and the heart. Pre-treatment with SAC (100 and 150 mg/kg) daily for a period of 45 days exhibited significant (P < 0.05) effect and altered these biochemical parameters positively. SAC (50, 100 and 150 mg/kg) treatment to normal rats did not exhibit any significant effect in any of the parameters studied. Thus, our study shows that SAC has a protective role in isoproterenol-induced myocardial infarction in rats. The observed effects might be due to the free radical scavenging, antioxidant and membrane stabilizing properties of SAC.
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PMID:Preventive effect of S-allylcysteine on membrane-bound enzymes and glycoproteins in normal and isoproterenol-induced cardiac toxicity in male Wistar rats. 1906 78

Schistosomiasis is one of the most important human parasitic diseases. One of the possible methods for the control is through the molluscan intermediate host of the parasite. Biomphalaria arabica, molluscan hosts to Schistosoma mansoni in Saudi Arabia were treated with sublethal concentrations (LC25) of dry powdered leaves Solanum nigrum. Effect of plant on ectonucleotidases (NTPdases) (ADPase & ATPase), sodium/potassium adenosine triphosphatase (Na+/K+ ATPase) and creatine kinase (CK) was traced. The plant molluscicide was potent in inhibiting the four investigated enzymes giving a percentage inhibition range between 45-55%. The effect of the inhibited enzymes on the compatibility of the snail hosts to schistosome parasite was discussed. In conclusion, the use of sublethal concentration of S. nigrum to disturb the biochemical profile of the snail hosts could be a promising and safe strategy to control the disease.
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PMID:Effect of plant molluscicides on selected enzymes related to energy metabolism in Biomphalaria arabica snails molluscan hosts to Schistosoma mansoni in Saudi Arabia. 2050 97

The aim of this investigation was to evaluate the preventive role of morin, a flavonoid, on cardiac marker enzymes such as aspartate transaminase, lactate dehydrogenase, creatine kinase and creatine kinase-MB, membrane-bound enzymes such as sodium potassium-dependent adenosine triphosphatase, calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase, and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with morin (20, 40 and 80 mg/kg) daily for a period of 30 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at an interval of 24 h for 2 days. ISO-induced rats showed significantly (P < 0.05) increased activities of cardiac marker enzymes in serum and decreased activities in the heart, and increased activities of calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase in the heart, and the activity of sodium potassium-dependent adenosine triphosphatase decreased in the heart. ISO induction also showed a significant increase in the levels of glycoproteins in serum and the heart. Pretreatment with morin (40 mg/kg) daily for a period of 30 days exhibited significant (P < 0.05) effects and altered these biochemical parameters positively compared to the other two doses. Thus, our study shows that morin has a protective role in ISO-induced MI in rats. The observed effects might be due to the free radical-scavenging, antioxidant and membrane-stabilising properties of morin.
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PMID:Pretreatment with morin, a flavonoid, ameliorates adenosine triphosphatases and glycoproteins in isoproterenol-induced myocardial infarction in rats. 2169 12

Several metals including barium (Ba) known as environmental pollutants provoke deleterious effects on human health. The present work pertains to the potential ability of selenium (Se) and/or vitamin C, used as nutritional supplements, to alleviate the toxic effects induced by barium chloride (BaCl2) in the heart of adult rats. Animals were randomly divided into seven groups of six each: group 1, serving as negative controls, received distilled water; group 2 received in their drinking water BaCl2 (67 ppm); group 3 received both Ba and Se (sodium selenite 0.5 mg kg-1 of diet); group 4 received both Ba and vitamin C (200 mg kg-1 bodyweight) via force feeding; group 5 received Ba, Se, and vitamin C; and groups 6 and 7, serving as positive controls, received either Se or vitamin C for 21 days. The exposure of rats to BaCl2 caused cardiotoxicity as monitored by an increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, a decrease in Na+-K+ adenosine triphosphatase (ATPase), Mg2+ ATPase, and acetylcholinesterase activities and in antioxidant defense system (catalase, glutathione peroxidase, superoxide dismutase, glutathione, and nonprotein thiols). Plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels increased, while high-density lipoprotein-cholesterol level decreased. Coadministration of Se and/or vitamin C restored the parameters indicated above to near control values. The histopathological findings confirmed the biochemical results. Se and vitamin C may be a promising therapeutic strategy for Ba-induced heart injury.
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PMID:Protective effects of dietary selenium and vitamin C in barium-induced cardiotoxicity. 2794 Nov 67


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