ROLE OF SODIUM-PUMP IN REGULATION OF LIVER METABOLISM IN EXPERIMENTAL ALCOHOLISM
ROLE OF SODIUM-PUMP IN REGULATION OF LIVER METABOLISM IN EXPERIMENTAL ALCOHOLISM
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DOI：
10.1111/j.1749-6632.1974.tb19117.x
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发表时间：
1974-01-01
影响因子：
5.2
通讯作者：
ISRAEL, Y
中科院分区：
文献类型：
--
作者：
BERNSTEIN, J;VIDELA, L;ISRAEL, Y
Ethanol is metabolized mainly in the liver1 by alcohol dehydrogenase (ADH) with the production of acetaldehyde, which is further metabolized to acetate?> In both these reactions NAD is reduced to NADH. The equilibrium constant for the reaction catalyzed by ADH favors the reduction of acetaldehyde to ethanol, but the oxidation of ethanol can proceed without accumulation of acetaldehyde because this compound is rapidly removed. NADH generated is reoxidized back to NAD mainly in the mitochondria. Since the mitochondrial membrane is impermeable to pyridine nucleotides, the reduced NADH is transported into the mitochondria by shuttle mechanism^!.^ It has been recently postulated that a large proportion of the acetaldehyde produced enters the mitochondria, where it is oxidized by a NAD-linked aldehyde dehydrogenase. 61 lZ8 We have proposed that the rate-limiting step in the oxidation of ethanol by liver tissue is the ability of the mitochondria to reoxidize the reducing equivalents produced? Both in vivo and in liver slices, mitochondrial uncouplers such as dinitrophenol (DNP) and arsenate are able to increase the rate of ethanol metabolism? i8 This increase is blocked by pyraz01e)~~ a well known inhibitor of ADH? In rats chronically treated with ethanol the rate of ethanol metabolism, as measured in liver slices, is increased (about 80%) to the levels obtained in control livers in the presence of mitochondrial uncouplers. This metabolism cannot be further increased by uncoupling agents.'The respiration of liver slices from these animals was also found to be increased (about 60%), but again DNP was not able to cause a further These results indicate that mitochondria in the liver of animals chronically treated with ethanol appear to be respiring at maximal rates. In this condition, the rate-limiting step for the oxidation of ethanol could still be the ability of mitochondria to reoxidize reducing equivalents. Conceivably, mitochondria could be respiring at maximal rates if they are either uncoupled or in a respiratory state closer to state 3 than to state 4.12We have studied several parameters in isolated mitochondria obtained from the livers of rats chronically treated with ethanol." In these mitochondria we did not observe changes in state 3 or state 4 respiration, respiratory control ratio (RCR), or DNP-uncoupled respiration, using either succinate or fl-hydroxybutyrate as substrates. There was, however, a very small but significant change in the ADP/O ratio with 0-hydroxybutyrate, but not with succinate. A reduction in ADP/O ratio without change in RCR could nevertheless occur if, in mitochondria of alcohol-treated animals, some endogenous substrates enter the respiratory chain at site 2 of oxidative phosphorylation. Indeed, we have observed that the respiration of these mitochondria, in the presence of ADP but in the absence of added substrates, is significantly higher than that of control mitochondria (unpublished data). The activity of mitochondrial adenosine triphosphatases (ATPases) was also measured. No changes were found after chronic
