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)

Although ethanol is known to exert its primary mode of action on the central nervous system, the exact molecular interaction underlying the behavioral and physiological manifestations of alcohol intoxication has not been elucidated. Chronic ethanol administration results in changes in organ functions. These changes are reflective of the adaptive mechanisms in response to the acute effects of ethanol. Biophysical studies have shown that ethanol in vitro disorders the membrane and perturbs the fine structural arrangement of the membrane lipids. In the chronic state, these membranes develop resistance to the disordering effects. Tolerance development is also accompanied by biochemical changes. Although ethanol-induced changes in membrane lipids have been implicated in both biophysical and biochemical studies, measurements of membrane lipids, such as cholesterol content, fatty acid unsaturation, phospholipid distribution, and ganglioside profiles, have not produced conclusive evidence that any of these parameters are directly involved in the action of ethanol. On the other hand, there is increasing evidence indicating that although ethanol in vitro produces a membrane-fluidizing effect, the chronic response to this effect is not to change the membrane bulk lipid composition. Instead, changes in membrane lipids may pertain to small metabolically active pools located in certain subcellular fractions. Most likely, these lipids are involved in important membrane functions. For example, the increase in PS in brain plasma membranes may provide an explanation for the adaptive increase in synaptic membrane ion transport activity, especially (Na,K)-ATPase. There is also evidence that the lipid pool involved in the deacylation-reacylation mechanism (i.e., PI and PC with 20:4 groups) is altered after ethanol administration. An increase in metabolic turnover of these phospholipid pools may have important implications for the membrane functional changes. Obviously, there are other lipid-metabolizing enzyme systems that may exert similar effects but have not yet been investigated in detail. From the results of these studies, it is concluded that the multiple actions of ethanol are associated with changes in enzymic systems important in the functional expression of the membranes.
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PMID:Ethanol and membrane lipids. 298 63

The acute effects of ethanol on the nervous system are thought to be associated with disturbance of neural membrane function. In the present study the effects of ethanol, its immediate metabolite, acetyldehyde, and tertiary butanol which is not further metabolized to an aldehyde, on selected membrane-bound enzymes were examined in vitro in rat brain. The enzymes included acetylcholinesterase, succinate dehydrogenase, Na+K+-ATPase and cytochrome c oxidase. At concentrations ranging from 0.07 - 2% w/v (15 - 435 mM) ethanol did not produce significant inhibition of any of the enzymes tested. On the other hand acetaldehyde at concentrations ranging from 0.01 - 0.5% w/v (2 - 114 mM) showed marked inhibition of all the abovementioned enzymes except acetylcholinesterase. The responses of the various enzymes to tertiary butanol were intermediate between those obtained with ethanol and acetaldehyde. Further studies are in progress to evaluate the significance of these findings to the understanding of alcohol intoxication, tolerance and dependence in man.
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PMID:Effect of ethanol and acetaldehyde on membrane-bound enzymes in rat brain. 742 41

Centrilobular hypoxia has been suggested to contribute to hepatic damage caused by alcohol intoxication. However, the mechanisms involved are still poorly understood. We have investigated whether alterations of Na(+) homeostasis might account for ethanol-mediated increase in hepatocyte sensitivity to hypoxia. Addition of ethanol (100 mmol/l) to isolated rat hepatocytes incubated under nitrogen atmosphere greatly stimulated cell death. An increase in intracellular Na(+) levels preceded cell killing and Na(+) levels in hepatocytes exposed to the combination of ethanol and hypoxia were almost twice those in hypoxic cells without ethanol. Na(+) increase was also observed in hepatocytes incubated with ethanol in oxygenated buffer. Ethanol addition significantly lowered hepatocyte pH. Inhibiting ethanol and acetaldehyde oxidation with, respectively, 4-methylpyrazole and cyanamide prevented this effect. 4-methylpyrazole, cyanamide as well as hepatocyte incubation in a HCO(3)(-)-free buffer or in the presence of Na(+)/H(+) exchanger blocker 5-(N,N-dimethyl)-amiloride also reduced Na(+) influx in ethanol-treated hepatocytes. 4-methylpyrazole and cyanamide similarly prevented ethanol-stimulated Na(+) accumulation and hepatocyte killing during hypoxia. Moreover, ethanol-induced Na(+) influx caused cytotoxicity in hepatocytes pre-treated with Na(+), K(+)-ATPase inhibitor ouabain. Also in this condition 4-methylpyrazole and 5-(N,N-dimethyl)-amiloride decreased cell killing. These results indicate that ethanol can promotes cytotoxicity in hypoxic hepatocytes by enhancing Na(+) accumulation.
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PMID:Ethanol potentiates hypoxic liver injury: role of hepatocyte Na(+) overload. 1106 92

We studied the effect of 2-week alcohol intoxication on water exchange and activity of Na,K-ATPase and Ca-ATPase in rat brain. Alcohol intoxication increased water content in the brain due to cell hyperhydration. It is assumed that hyperhydration results from increased Na+ content in cells due to inhibition Na,K-ATPase activity, which in turn is caused by activation of lipid peroxidation under the effect of ethanol. A possible mechanism of Na,K-ATPase inhibition.
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PMID:Effect of alcoholic intoxication on water content and activity of Na,K-ATPase and Ca-ATPase in rat brain. 1266 Aug 32