Abstract
Gastric intubation of female Sprague-Dawley rats (80–150 g) with one large dose (5 g/kg) of ethanol nearly doubled oxygen uptake of the isolated, perfused rat liver in only 2.5 hours. This increased hepatic respiration can account for the Swift Increase in Alcohol Metabolism (SIAM). Inhibition of enhanced oxygen and ethanol uptake by KCN (2 mM) and 4-methylpyrazole (0.8 mM) indicated the involvement of the mitochondrial respiratory chain and alcohol dehydrogenase in this phenomenon, respectively.
Epinephrine (2 mg/kg, i.p.) mimicked the increase in respiration observed with ethanol; however, the effects of epinephrine and ethanol were not additive. Pretreatment with α- or β-adrenergic blocking agents, hypophysectomy and adrenalectomy prevented the increase in oxygen and ethanol uptake due to ethanol treatment. These data suggest that hormones including epinephrine are involved in the mechanism of SIAM. Hormone action in all liklihood activates a number of metabolic ATPase activities which lead to elevated oxygen uptake. One such process involved in the activation of oxygen uptake is diminished glycolysis, a ATP producing reaction sequence. The ADP not phosphorylated in the cytosol then enters the mitochondria where it stimulates oxygen uptake and NADH reoxidation. This ultimately leads to an acceleration of ADH-dependent ethanol metabolism.
Supported, in part, by AA-03624 and ARA-7905.
Recipient of Research Career Development Award AAA-00033.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bergmeyer, H.U., 1970, in: Methoden der Enzymatischen Analyse Verlag Chemie, Weinheim.
Bernstein, J., L. Videla, and Y. Israel, 1973, Metabolic alterations produced in the liver by chronic alcohol administration. II. Changes related to energetic parameters of the cell, Biochem. J., 134:515.
Bleyman, M.A., and R.G. Thurman, 1979, Comparison of acute and chronic ethanol administration on rates of ethanol elimination in the rat in vivo, Biochem. Pharmacol. 28:2027.
Chance, B., and G.R. Williams, 1955, A method for localization of sites for oxidative phosphorylation, Nature 176: 250.
DeCarli, L.M., and C.S. Lieber, 1967, Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet, J. Nutr. 91:331.
Israel, Y., L. Videla, A. MacDonald, and J. Bernstein, 1973, Metabolic alterations produced in the liver by chronic alcohol administration. III. Comparison between the effects produced by ethanol and by thyroid hormones, Biochem. J., 134:523.
Mendelson, J., S. Stein, and N. Mello, 1965, Effects of experimentally induced intoxication of ethanol -1-C14 in alcohol subjects, Metabolism 14: 1255.
Porta, E.A., and C.L.A. Gomez-Dumm, 1968, A new experimental approach in the study of chronic alcoholism. I. Effects of high alcohol intake in rats fed a commercial laboratory diet, Lab. Invest. 18:352.
Rawat, A.K., and F. Lundquist, 1968, Influence of thyroxine on the metabolism of ethanol and glycerol in rat liver slices, Eur. J. Biochem. 5:13.
Scholz, R., W. Hansen, and R.G. Thurman, 1973, Interaction of mixed-function oxidation with biosynthetic processes. I. Inhibition of gluconeogenesis by aminopyrine in perfused rat liver, Eur. J. Biochem. 38:64.
Thurman, R.G., W.R. McKenna, and T.B. McCaffrey, 1976, Pathways responsible for the adaptive increase in ethanol utilization following chronic treatment with ethanol: Inhibitor studies with the hemoglobin-free perfused rat liver, Mol. Pharmacol. 12:156.
Thurman, R.G., and R. Scholz, 1976, Ethanol metabolism in perfused rat liver at low ethanol concentrations: Involvement of alcohol dehydrogenase in the adaptive increase in ethanol metabolism due to chronic pretreatment with ethanol, Hoppe-Seyler’s Z. Physiol. Chem. 357:1443.
Thurman, R.G., and R. Scholz, 1977, Interaction of glycolysis and respiration following the addition of ethanol, Eur. J. Biochem. 750:13.
Videla, L., J. Bernstein, and Y. Israel, 1973, Metabolic alterations produced in the liver by chronic alcohol administration. Increased oxidative capacity, Biochem. J., 134:507.
Wendell, G.D., and R.G. Thurman, 1979, Effect of ethanol concentration on rates of ethanol elimination in normal and alcohol-treated rats in vivo, Biochem. Pharmacol. 28:273.
Yuki, T., and R.G. Thurman, 1980, The swift increase in alcohol metabolism. Time course for the increase in hepatic oxygen uptake and the involvement of glycolysis, Biochem. J., 184:119
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1980 Springer Science+Business Media New York
About this chapter
Cite this chapter
Yuki, T., Thurman, R.G. (1980). Mechanism of the Swift Increase in Alcohol Metabolism (“SIAM”) in the Rat. In: Thurman, R.G. (eds) Alcohol and Aldehyde Metabolizing Systems-IV. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1419-7_71
Download citation
DOI: https://doi.org/10.1007/978-1-4757-1419-7_71
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-1421-0
Online ISBN: 978-1-4757-1419-7
eBook Packages: Springer Book Archive