Rate-Determining Factors for Ethanol Metabolism in Vivo during Fasting
Fasting produces a decrease in ethanol elimination rate of as much as 40% in rats and hamsters. In order to identify the biochemical process responsible for this change, the maximal activity of ADH, the cytosolic free NAD+/NADH ratio and the concentration of ethanol and acetaldehyde in liver were measured in both fed and 48 h fasted rats and hamsters after ethanol administration. While the maximal ADH activity of liver decreased 40% or more with fasting, only a small difference in NAD+/NADH ratio was observed between fed and fasted animals both 1 and 2 h following the administration of ethanol. Calculations of the steady-state rates of oxidation of ethanol by rat ADH revealed that the enzyme is rate-limited primarily by the concentration of free NAD+ in cytosol but that the steady-state rates of ethanol oxidation by ADH are 80–90% of the in vivo ethanol elimination rates. With fasting, the percentage decrease in steady-state rates was identical to that for ADH activity and for the in vivo elimination rate. These results indicate that changes in rates of oxidation of NADH and acetaldehyde contribute little toward the decrease in ethanol elimination rate associated with fasting but that the change in liver ADH activity or content is primarily responsible.
KeywordsElimination Rate Ethanol Administration Ethanol Metabolism Alcohol Metabolism NADH Ratio
Unable to display preview. Download preview PDF.
- Büttner, H., 1965, Aldehyd- und alkoholdehydrogenase-aktivitat in leber und niere der ratte, Biochem. Z., 341: 300.Google Scholar
- Cornell, N.W., Crow, K.E., Leadbetter, M. et al., 1978, Kinetics of alcohol dehydrogenase and the rate of ethanol metabolism in the rat in vivo, Fed. Proc., 37: 1605.Google Scholar
- Eriksson, C.J.P., Sippel, H.W., and Forsander, O.A., 1975, Factors influencing the determination of acetaldehyde in biological samples by head-space gas chromatography, in: “The Role of Acetaldehyde in the Actions of Ethanol,” K.O. Lindros and C.J.P. Eriksson, ed., The Finnish Foundation for Alcohol Studies, Helsinki.Google Scholar
- Gutmann, I., and Wahlefeld, A.W., 1974, L-(+)-Lactate: Determination with lactate dehydrogenase and NAD, in: “Methods of Enzymatic Analysis,” H.U. Bergmeyer, ed., Academic Press, New York.Google Scholar
- Le Breton, E., 1936, Influence du jeune sen la vitesse d’oxydation de l’alcool ethylique chez le rat blanc, Compt. Rend. Soc. Biol., 122: 330.Google Scholar
- Lieber, C.S., 1977, “Metabolic Aspects of Alcoholism,” University Park Press, Baltimore.Google Scholar
- Mirsky, I.A., and Nelson, N., 1939, The influence of the pancreas and the liver on the oxidation of ethyl alcohol, Am. J. Physiol., 127: 308.Google Scholar
- Passonneau, J.V., and Lowry, O.H., 1974, Pyruvate: Fluorometric assay, in: “Methods of Enzymatic Analysis,” H.U. Bergmeyer, ed., Academic Press, New York.Google Scholar
- Widmark, E.M.P., 1932, Die theoretischen grundlagen und die praktische Verwenbarkeit der gerichtlich-medizinischen alkoholbestimmung, Urban and Schwarzenberg, Berlin.Google Scholar