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 02 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 f-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 Mg2+-activated adenosine triphosphatase, dinitrophenol-activated adenosine triphosphatase or in the dinitrophenol-activated adenosine triphosphatase/Mg2+-activated adenosine triphosphatase ratio were found as a result of the chronic ethanol treatment. 4. Liver microsomal NADPH oxidase activity, a H202-producing system, was increased by 80-100 % by chronic ethanol treatment. Oxidation offormate to CO2 in vivo was also increased in these animals. The increase in formate metabolism could theoretically be accounted for by an increased production of H202 by the NADPH oxidase system plus formate peroxidation by catalase. However, an increased production of H202 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 02 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.Previous studies by our group (Videla & Israel, 1970) indicate that the rate of ethanol metabolism by the liver depends on the rate of mitochondrial reoxidation of the cytoplasmic NADH produced in the oxidation of ethanol. Uncoupling agents such as 2,4-dinitrophenol or arsenate were shown to increase markedly the rate of ethanol metabolism by normal rat liver slices. Dinitrophenol was also shown to be effective in increasing the rate of ethanol metabolism in vivo . However, although dinitrophenol increased the ethanol metabolism in liver slices from control animals, it was not effective in those from animals chronically treated with ethanol, in which the rate of ethanol metabolism had already been increased. This suggested that the rate ofethanol metabolism in these animals was no longer ...

1. Chronic ethanol administration to rats for 21-27 days increases the rate of O(2) consumption as measured in liver slices. The extra respiration can be abolished by inhibition of the active transport of Na(+) and K(+). Dinitrophenol activates the respiratory rate in the liver of the treated animals only in the presence of ouabain. 2. Active (ouabain-sensitive) transport of (86)Rb and (Na(+)+K(+))-stimulated adenosine triphosphatase activity were increased in the livers of the ethanol-treated animals. 3. Chronic ethanol administration also led to a decrease in the phosphorylation potential ([ATP]/[ADP][P(i)]) in the liver cell owing to a decrease in [ATP] and an increase in [P(i)]. 4. It is suggested that an increased sodium pump activity is responsible for the increased oxidative capacity and for the insensitivity to dinitrophenol observed in the livers of ethanol-treated animals.

1. Liver slices from rats treated with thyroxine show an increased rate of O(2) consumption. The extra consumption, but not the basal respiration, can be abolished by ouabain. 2. Dinitrophenol is not effective in increasing the rate of O(2) consumption of liver slices from thyroxine-treated animals but its effectiveness can be recovered in the presence of ouabain. 3. (Na(+)+K(+))-stimulated adenosine triphosphatase activity of liver was increased by administration of thyroxine in vivo. No changes were found in total Mg(2+)-stimulated adenosine triphosphatase activity. 4. Mitochondrial alpha-glycerophosphate dehydrogenase and microsomal NADPH oxidase activity were increased by both thyroxine and chronic ethanol treatment. 5. Liver slices from animals chronically treated with ethanol synthesize urea at an increased rate. 6. Mitochondrial size (section area) is markedly increased in the liver of animals chronically treated with ethanol. 7. Acute administration of ethanol in doses of 4 and 6g/kg significantly increases the uptake of (131)I-labelled thyroxine by the liver. 8. Work reported here, along with results from other investigators, indicates marked similarities between the effects produced in the liver by chronic administration of ethanol and by thyroid hormones.

Red cells of newborn calves contain 105-110 mmole K + and 1-5 mmole Na+ per liter of cells. As the animals age the K+ content decreases. to a value of 25-30 mmole/liter of cells after about 60 days. At approximately the same time, the sodium content reaches a value of 60-70 mmole/liter. The time required for half change (tl/2) is 35-37 days for both Na + and K + . The activity of (Na + K)-adenosine triphosphatase (ATPase) and the influx of K 4 2 and Rb 86 into the red cells are high at birth and are reduced to 5 and 15 % of their original values, respectively, in mature animals. t2 for both is of the order of 30-35 days. The membrane Mg-ATPase activity is also high at birth and is reduced with a t/2 of 28-32 days to a final value of about 20 % of its activity at birth. Separation of red cells according to their age showed that, in animals at the age of transition, newly formed red cells contain a higher K/Na ratio and a higher active transport capacity than older red cells of the same animal. It is suggested that the changes observed are a reflection of the average age of the red cell population as the animal grows.

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