The Role of Hydrogen Translocating Shuttles during Ethanol Oxidation in Hepatocytes from Euthyroid and Hyperthyroid Rats

Abstract

A quantitative study of the contribution of the malate-aspartate and glycerol-3-phosphate cycles to the translocation of reducing equivalents from cytosol to mitochondria during ethanol oxidation has been made in hepatocytes from euthyroid and hyperthyroid rats.1. In hepatocytes from euthyroid rats both cycles have an almost equal capacity and their relative contribution to total hydrogen transport to the mitochondria depends on the conditions chosen.2. In hepatocytes from hyperthyroid rats maximal rates of ethanol oxidation were significantly lower than in hepatocytes from euthyroid rats, even though the capacity of the glycerol-3-phosphate cycle was increased. This was due to a decreased activity of alcohol dehydrogenase.Three factors can control the rate of hepatic ethanol oxidation : firstly, the activity of alcohol dehydrogenase; secondly, the translocation of reducing equivalents from cytosol to mitochondria; and thirdly, the oxidation of mitochondrial reducing equivalents by oxygen. Depending on the experimental conditions each of these factors can be rate-limiting for ethanol oxidation [l -61. Of the various possible shuttle systems involved in the transport of reducing equivalents from cytosol to mitochondria the malate-aspartate and the glycerol-3-phosphate cycles are presumably quantitatively the most important ones (see [7,8] for reviews). There is, however, no general agreement about the relative importance of these two shuttles during ethanol oxidation. According to Berry and coworkers [5,9] the malate-aspartate cycle plays only a minor role in ethanol oxidation. However, in other reports the contrary is stated [1-3,lO-131. In this paper we describe a quantitative study of the contribution of the malate-aspartate and glycerol-3-phosphate cycles to the translocation of reducing

The capacity of reducing‐equivalent shuttles limits glycolysis during ethanol oxidation

“…g-', which was almost doubled when ethanol was also present ( Table 1). This latter transfer rate is considerably less than the maximal hepatic shuttle capacity [27,281 and can be accounted for on the basis of the loss of shuttle components by the isolated hepatocytes during their preparation [29].…”

Effect of age increase on metabolism and toxicity of ethanol in female rats

“…In both human and rodents, alcohol dehydrogenase (ADH) has a primary role in the metabolism of ethanol, however, activity of this enzyme is not the sole rate limiting factor in the elimination of ethanol in vivo. Under certain conditions availability of oxidized nicotinamide adenine dinucleotide (NAD + ), the cofactor for the ADH reaction, becomes rate limiting (Meijer et al, 1975;Berry and Kun, 1978;Hensgens et al, 1980). It is also known that cytochrome P-450-dependent microsomal ethanol oxidizing system (MEOS) has a significant role in the metabolism of ethanol at high concentrations (Lieber, 1994).…”

Control of ammonia distribution ratio across the liver cell membrane and of ureogenesis by extracellular pH

“…From the above considerations, is appears that CPS activity could be almost immediately enhanced by small changes in ammonia availability (in complement to effects of N-acetylglutamate which are slower to operate [33]). Owing to the high concentrations of CPS in mitochondria, such a feature probably endows hepatocytes with a large spare capacity to remove circulating ammonia, even in the presence of portal hyperammoniemia, but this process is particularly sensitive to disturbances of acid-base equilibrium.…”