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)

1 The specific [3H]-ouabain binding to microsomal fractions derived from cat heart, liver, spleen, and kidney increased significantly following chronic administration of ethanol. 2 Since ouabain binds exclusively to cell membrane (Na+ + K+)-adenosine triphosphatase ((Na+ + K+)-ATPase), these results provide evidence for an increase in number of (Na+ + K+)-ATPase macromolecules during chronic alcoholism. 3 The importance of the increase in number of (Na+ + K+)-ATPase molecules in the adaptive increase in ethanol metabolism and cardiac myopathy in chronic alcoholism is discussed.
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PMID:[3H]-Ouabain binding to peripheral organs of cats: effect of ethanol. 14 33

Programmed-feeding polydipsia results in a reliable model of chronic alcoholism in the rat. High oral ethanol comsumption and a predictable withdrawal reaction associated with audiogenic seizures are produced. The maintenance of high blood ethanol levels for three weeks in 18 male Charles River rats was associated with audiogenic seizures after 6 or 8 hours of withdrawal. These chronic alcoholic rats had enhanced blood clearance of ethanol. The cerebral cortical crude mitochondrial fraction showed a decrease in total and magnesium-dependent adenosine triphosphatase activity in alcoholic and control (water-fed) rats compared with normal rats.
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PMID:Programmed feeding as a model of chronic alcoholism in the rat. 15 1

Magnesium is an essential cofactor for many enzymatic reactions, especially those involved in energy metabolism. Deficits of magnesium are prevalent due to inadequate intake or malabsorption and due to the renal loss of magnesium that occurs in certain disease states (alcoholism, diabetes) and with drug therapy (diuretics, aminoglycosides, cisplatin, digoxin, cyclosporin, amphotericin B). Protracted deficits of magnesium in humans and animals result in neurological disturbances, including hyperexcitability, convulsions and various psychiatric symptoms ranging from apathy to psychosis, some of which can be reversed with magnesium supplementation, others requiring correction of the dysregulation mechanism. Although the role of magnesium in neuronal function is not completely understood, a lowering of CSF or brain magnesium can induce epileptiform activity and there is an association between decreased CSF magnesium and the development of seizures. CSF concentrations of magnesium are normally higher than magnesium plasma ultrafiltrate (diffusible) concentrations due to the active transport of magnesium across the blood-brain barrier. Under conditions of magnesium deficiency, CSF concentrations decline, although this decline lags behind and is less pronounced than the changes observed in plasma magnesium concentrations. Decreases in CSF magnesium concentrations correlate with the alterations observed in extracellular brain magnesium concentrations in animals following the dietary deprivation of magnesium. CSF magnesium concentrations can readily be repleted following magnesium supplementation, although high dose magnesium therapy, such as that used in the treatment of convulsions in eclampsia, will only increase CSF magnesium concentrations to a very limited degree (approximately 11-18 per cent) above physiological concentrations. Greater increases in CSF magnesium may occur in neonates since neonatal swine, following treatment with magnesium, have CSF magnesium concentrations that are similar to their plasma concentrations. There has been a recent resurgence of interest in magnesium deficiency and its neurological consequences due to the finding that magnesium, at physiological concentrations, blocks N-methyl-D-aspartate (NMDA) receptors in neurones. NMDA receptors are normally activated by glutamate and/or aspartate which represent the principal neurotransmitters for excitatory synaptic transmission in vertebrate CNS. Magnesium deficiency produces epileptiform activity in the CNS which can be blocked by NMDA receptor antagonists. Other mechanisms, including alterations in Na+/K(+)-ATPase activity, cAMP/cGMP concentrations and calcium currents in pre- and postsynaptic membranes, may also be at least partially responsible for the neuronal effects associated with low brain magnesium. Further studies are necessary to increase our understanding of the neurological implications of magnesium deficit in the central nervous system.
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PMID:Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. 129 67

Several alterations of the small-intestinal morphology and function have been documented after alcohol ingestion. There are morphologic changes macroscopically and microscopically after acute alcohol administration in the proximal part of the small intestine, which are quickly reversible. There are no macroscopic changes and, in most patients, very discrete light microscopic changes in the small intestine after chronic alcohol ingestion. The ultrastructural changes are, however, profound, as seen by both transmission and scanning electron microscopy. The permeability is probably increased, permitting entrance of possible noxious agents, which may explain some of the extraintestinal tissue damage observed in chronic alcoholism. The transit is increased, at least after acute alcohol administration, perhaps contributing to the diarrhea commonly seen after heavy drinking. Several of the enzymes located in the brush border are affected; lactase activity can be depressed and perhaps result in a transient milk intolerance in predisposed individuals. The activity of GGT is increased and may partly account for the GGT elevation in serum after heavy drinking. Other enzymes, such as Na(+)-K(+)-ATPase, can be inhibited and result in a decreased absorption of substances that require active, energy-dependent transport mechanisms. The secretion of water and electrolytes may be increased (an effect on cAMP?). The absorption of several nutrients, vitamins, and other elements is disturbed. The bacterial flora is increased and changed, which may give rise to symptoms and also increase the production of acetaldehyde by bacterial metabolism of ethanol. Acetaldehyde is more toxic than ethanol, and an increased concentration of acetaldehyde can possibly accentuate the damage to the liver and other organs. The bacterial overgrowth can possibly cause endotoxinemia. Although studies on alcohol-related intestinal alterations have been relatively sparse, the acute and chronic effects of alcohol thus seem to be considerable. From available results it is, however, difficult to draw any definite conclusions about the clinical importance of many of the findings. Future research will need to study the relationship between, for example, the chronic morphologic changes, the absorptive dysfunction, and permeability alterations, on the one hand, and the gastrointestinal symptoms, the extraintestinal damage, and various deficiencies, on the other hand.
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PMID:Alcohol and the small intestine. 200 95

The autopsy report of an asymptomatic, non familial cardiomyopathy with widespread fatty infiltration of the right ventricular wall in two alcoholic subjects, who were also heavy smokers and suffering from a serious laryngeal obstruction, led the Authors to investigate, on the basis of a thorough review of the literature, the possibility that hypoxia, alcoholism and smoke could have caused the development of the cardiac lesion. The presence of myocardial fatty infiltration is explained, under conditions of high-flow hypoxia, by the reduced fatty acid oxidation. The higher tissue levels of fatty acyl-CoA, fatty acyl-carnitine and alpha-glycerophosphate thereby lead to the increased conversion of the FFA into tissue lipids. Under hypoxic conditions there is also an increased polyols synthesis. The reduced conversion of dyacylglycerol into phosphatidic acid causes its tissutal increase and the interaction with fatty acyl-CoA to produce triacylglycerol and CoASH. In alcoholic patients reduced oxidation and increased FFA synthesis is sustained by the altered mitochondrial respiratory control and excess of acetate, with the consequent increase in acetyl-CoA, fatty acyl-CoA and alpha-glycerophosphate concentration. In addition, fatty acid ethyl esters normally absent in the myocardium are formed. The fact that, in hypoxic or alcoholic subjects with cardiomyopathy, an impaired myocardial contractility has been noted as the most relevant haemodynamic factor may be explained by both the reduced energy production following the decrease in aerobic glycolysis and FFA oxidation, and specific genetic changes that lead to both the production of a myosin with lower Ca2 + ATPase activity and a reduced protein (and therefore myofibrillar) synthesis. This fact can result in a severe atrophy of the cardiac myocytes. The lower their contractile activity, the more evident the process of atrophy. The lesion principally affects the right ventricle for both metabolic and anatomical reasons. It has been shown how, under normal conditions, the RV metabolism is suited to a relatively reduced O2 supply situation, with a high lactate dehydrogenase and alpha-hydroxybutiratedehydrogenase activity. It is more likely to be affected therefore whenever there is a chronic state of high-flow hypoxia. While alpha-HBDH allows the RV extensive utilization of ketone bodies as an energy source, its notable increase under hypoxic conditions further increases the synthesis of fatty acids and therefore fatty infiltration of the myocardium. The relatively lower capacity for oxygen extraction and lower tissue perfusion of the RV compared with the left ventricle make an adequate oxygen supply in the case of increased O2 demand even more difficult.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hypoxic right ventricular cardiomyopathy. A morphological and pathogenetic study on the myocardial atrophy and fatty infiltration. 209 33

Erythrocyte ouabain-inhibitable sodium pump activity, a measure of NaK-ATPase activity, was studied in 6 diagnostic groups of psychiatric subjects: bipolar affective disorder, unipolar depressive disorder, neurotic depression, chronic alcohol abuse, schizoaffective disorder, and schizophrenia, and in sex- and age-matched normal controls. In the bipolar manic-depressive group, which was restricted to lithium-free subjects, values for sodium pump activity were significantly lower than in the controls (-11.4%, n = 53, p less than 0.001); subgrouping of the bipolar group by sex or age showed a significantly lower sodium pump activity in each of the groups. In the unipolar depressive group, values for sodium pump activity were significantly higher than in the controls (+13.7%, n = 12, p less than 0.01). The difference in direction of changed sodium pump activity between the bipolar and the unipolar groups was also observed in the values for subgroups of subjects in the two categories who were in a depressed state at the time the blood sample was taken. In the chronic alcohol abuse group, values for sodium pump activity were significantly higher than those for the control group (+13.5%, n = 20, p less than 0.05). In the neurotic depression (n = 24), schizoaffective (n = 12), and schizophrenia (n = 35) groups, there were no significant differences in sodium pump activity between the group of psychiatric subjects and their matched controls. These observations indicate that there is a trait-dependent deficiency of NaK-ATPase activity in bipolar affective disorder.
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PMID:Erythrocyte sodium pump activity in bipolar affective disorder and other psychiatric disorders. 256 81

The role of mitochondria in the initiation or promotion of pancreatic pathologic conditions has not been clearly delineated. In this context, it has recently been suggested that abnormal mitochondrial function may account for the fat accumulation observed in pancreatic acinar cells in alcoholism. To study these issues, we developed a method for the isolation of functional mitochondria from the rat pancreas. The resultant mitochondrial pellet possessed oligomycin-insensitive Mg2+-adenosine triphosphatase (ATPase) activity, and coupled respiration could be demonstrated in the presence of EDTA only after Mg2+ had been excluded from the incubation medium. Albumin was also a requirement for the demonstration of coupled respiration in vitro. When this new technique was applied to a rat model of alcohol-induced pancreatic steatosis, no mitochondrial dysfunction was demonstrated, suggesting that some other mechanism is responsible for fat accumulation in pancreatic acinar cells after long-term ethanol consumption. In contrast, DL-ethionine administration to rats produced partial or total uncoupling of mitochondrial respiration in the absence of morphologic evidence of mitochondrial injury.
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PMID:New technique for the isolation of functional rat pancreatic mitochondria and its application to models of pancreatic injury. 293 90

Eleven patients diagnosed and treated for congestive cardiomyopathy (COCM) of unknown aetiology, and another 10 patients, with congestive alcoholic heart muscle disease (ACOCM) were studied. Muscle biopsy samples were obtained from the vastus lateralis (VL) and the gastrocnemius (G) muscles. In part of the sample muscle the fibre pattern was classified by means of ATPase activity staining, a technique based on the pH lability of the fibres concerned. Fibre typing and area measurements were carried out by light microscope. The other part of the sample was used as muscle homogenate of which the Ca2+-activated ATPase activity as well as citrate synthetase (CS) and aldolase activities were measured. No significant difference was found in these enzyme activities between the two groups of patients. The proportion of the slow twitch (ST) fibres in the VL, mainly in the patients with ACOCM, was lower as compared to data for healthy subjects. A similar tendency was revealed for G. In both muscles tested, the area of ST fibres was smaller in the ACOCM group. The fast twitch (FT) fibre area proved to be slightly different in the two groups of subjects tested. Occurrence of degenerative signs in the histological tests was higher in the ACOCM than in the COCM group. It was concluded that differences in the skeletal muscles of patients with ACOCM and COCM may primarily account for the alcoholism. The disease of the heart muscle has little effect on the function of skeletal muscle. Even so, a low amount or lack of physical activity may have an unfavourable influence on the skeletal muscles of patients with heart muscle disease.
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PMID:Skeletal muscle biopsy studies of cardiac patients. 296 68

The ability to induce alcoholic cardiomyopathy has been tested in a variety of animal species. Myocardial alterations consistent with subclinical heart disease have been produced in many of these studies through a direct effect of ethanol or its metabolites upon the heart or a neurohumoral mechanism. In the rat most studies have, however, failed to finding diminished contractility in the basal state. In long-term animals the acute left ventricular responses to isoproterenol and calcium as well as pacing were reduced. Long-term studies in mongrel dogs fed 36 per cent of calories as ethanol produced an early decrease in left ventricular diastolic compliance related to interstitial collagen accumulation. Diminished contractility developed by four years. In addition to the morphologic evidence of distorted sarcoplasmic reticulum, in vitro experiments suggest important acute effects. Each mole of ethanol is bound tightly to each mole of protein comprising the Ca-ATPase pump, which is inhibited. Impaired uptake and binding of calcium by the sarcoplasmic reticulum has been observed in chronic alcohol models at one to two day intervals following the last exposure to ethanol. In addition, the flux of calcium ion does not appear normal in terms of access to contractile protein, where the calcium regulated inhibition of the troponin interaction with myosin is impaired. Experimental studies in a canine model of alcoholism revealed that the ventricular fibrillation threshold was moderately reduced in the basal state after 18 months and was diminished further after acute exposure.
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PMID:Experimental models for studying the effects of ethanol on the myocardium. 331 64

In the United States and other developed countries thiamin deficiency is often related to chronic alcoholism. A number of mechanisms may be involved in the pathogenesis of thiamin deficiency in the alcoholic population. An important cause is inadequate intake of thiamin. Moreover, there may be decreased converstion of thiamin to the active coenzyme, reduced hepatic storage of the vitamin in patients with fatty metamorphosis, ethanol inhibition of intestinal thiamin transport, and impaired thiamin absorption secondary to other states of nutritional deficiency. The present discussion focuses on the mechanism of ethanol-related thiamin malabsorption. Under normal conditions thiamin transport in animals and humans is biphasic. At low or physiological thiamin concentrations, transport is a saturable, carrier-mediated, active process; but at higher concentrations, the transport of thiamin is predominantly passive. Ethanol reduces the rate of intestinal absorption and the net transmural flux of thiamin. Furthermore, ethanol inhibits only the active and not the passive component of thiamin transport by impeding the cellular exit of thiamin across the basolateral or serosal membrane. The impairment of thiamin movement out of the enterocyte correlates with a fall in the activity of Na-K ATPase. Bound to the basolateral membrane, Na-K ATPase is believed to be involved in the kinetics of active transport. Ethanol also increases the fluidity of enterocyte brush border and basolateral membranes. Since ethanol increases membrane fluidity it is possible that tahe impairment of thiamin transport and the diminution of Na-K ATPase activity may be related, at least partly, to a physical perturbation of the enterocyte membrane.
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PMID:Mechanisms of thiamin deficiency in chronic alcoholism. 625 54


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