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

The concept of a hypermetabolic state to explain metabolic tolerance to ethanol grew from the recognition that the rate of alcohol metabolism is, in general, limited by the rate at which mitochondria can reoxidize reducing equivalents and thus by the rate at which oxygen can be consumed by the liver. This relationship appears to be most important in conditions in which the alcohol dehydrogenase (ADH)/QO2 ratio is high and is not in conflict with observations suggesting that ADH can, under certain conditions, constitute a rate-determining step for ethanol metabolism in rodents. Liver preparations from animals fed alcohol chronically, in which an increase in ethanol metabolism is shown, consume oxygen at higher rates. This effect, concerning which there is discrepancy among investigators, depends on the type of preparation. Thyroid hormones play a permissive role in the development of the hypermetabolic state, while increased circulating levels of these hormones are not required. Antithyroid drugs inhibit both metabolic tolerance in vivo and the hypermetabolic state. While the hypermetabolic state requires an increased ATP utilization in the form of an adenosine triphosphatase, or an inhibition of ATP synthesis, the different mechanisms proposed for such an effect do not quantitatively account for the increases in oxygen consumption. In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced. In some situations, low oxygen tensions in zone 3 of the hepatic acinus can reach critical hypoxic levels and may lead to cell necrosis. Studies in which the effectiveness of propylthiouracil is tested in human alcoholic hepatitis are discussed.
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PMID:Hypermetabolic state and hypoxic liver damage. 632 88

The activities of 13 liver and 6 brain enzymes were studied in 7-12 week old CD2F1 male mice that had been fed ad libitum and standardized either to 12 hours of light (0600-1800) alternating with 12 hours of darkness (1800-0600) (LD12:12); or to a reversed light-dark cycle (darkness 0600-1800; light 1800-0600) (DL12:12). Three separate studies were performed on two different days; in each experiment, subgroups of 14 animals were sacrificed at 3-hour intervals. Livers were assayed for: isocitrate dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, glutathione reductase, glyoxylate reductase, L-alanine aminotransferase, glutamate oxalacetate transaminase, pyruvate decarboxylase, fructose-1-phosphate aldolase, fructose diphosphate aldolase, fructose 1,6-diphosphatase, and fatty acid synthetase. Brains were assayed for phosphoglucose isomerase, adenosine triphosphatase, creatine phosphokinase, pyruvate kinase, adenylate kinase, and malate dehydrogenase. All 19 enzymes demonstrated a prominent circadian rhythm in at least one experiment. Moreover, each rhythmic variable showed a statistically significant fit to a 24-hour cosine (sine) curve by the method of least squares. In general, peak activities of the liver enzymes analyzed were associated with the beginning of the dark cycle and initiation of the animal's activity, while the group of brain enzymes had peak activities which occurred at the beginning of the animals' rest span and were near the beginning of the light cycle. The phasing of each of the rhythms could be reversed within a two-week span after reversing the environmental light-dark cycle 180 degrees.
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PMID:Circadian organization of thirteen liver and six brain enzymes of the mouse. 731 49

1. Administration of ethanol (14g/day per kg) for 21-26 days to rats increases the ability of the animals to metabolize ethanol, without concomitant changes in the activities of liver alcohol dehydrogenase or catalase. 2. Liver slices from rats chronically treated with ethanol showed a significant increase (40-60%) in the rate of O(2) consumption over that of slices from control animals. The effect of uncoupling agents such as dinitrophenol and arsenate was completely lost after chronic treatment with ethanol. 3. Isolated mitochondria prepared from animals chronically treated with ethanol showed no changes in state 3 or state 4 respiration, ADP/O ratio, respiratory control ratio or in the dinitrophenol effect when succinate was used as substrate. With beta-hydroxybutyrate as substrate a small but statistically significant decrease was found in the ADP/O ratio but not in the other parameters or in the dinitrophenol effect. Further, no changes in mitochondrial Mg(2+)-activated adenosine triphosphatase, dinitrophenol-activated adenosine triphosphatase or in the dinitrophenol-activated adenosine triphosphatase/Mg(2+)-activated adenosine triphosphatase ratio were found as a result of the chronic ethanol treatment. 4. Liver microsomal NADPH oxidase activity, a H(2)O(2)-producing system, was increased by 80-100% by chronic ethanol treatment. Oxidation of formate to CO(2)in vivo was also increased in these animals. The increase in formate metabolism could theoretically be accounted for by an increased production of H(2)O(2) by the NADPH oxidase system plus formate peroxidation by catalase. However, an increased production of H(2)O(2) and oxidation of ethanol by the catalase system could not account for more than 10-20% of the increased ethanol metabolism in the animals chronically treated with ethanol. 5. Results presented indicate that chronic ethanol ingestion results in a faster mitochondrial O(2) consumption in situ suggesting a faster NADH reoxidation. Although only a minor change in mitochondrial coupling was observed with isolated mitochondria, the possibility of an uncoupling in the intact cell cannot be completely discarded. Regardless of the mechanism, these changes could lead to an increased metabolism of ethanol and of other endogenous substrates.
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PMID:Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity. 1674 11