Steady-state kinetic properties of purified rat liver alcohol dehydrogenase: Application to predicting alcohol elimination rates in vivo

David Crabb, William F. Bosron, Ting Kai Li

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The rate of ethanol elimination in fed and fasted rats can be predicted based on the liver content of alcohol dehydrogenase (EC 1.1.1.1), the steady-state rate equation, and the concentrations of substrates and products in liver during ethanol metabolism. The specific activity, kinetic constants, and multiplicity of enzyme forms are similar in fed and fasted rats, although the liver content of alcohol dehydrogenase falls 40% with fasting. The two major forms of the enzyme were separated and found to have very similar kinetic properties. The rat alcohol dehydrogenase is subject to substrate inhibition by ethanol at concentrations above 10 mm and follows a Theorell-Chance mechanism. The steady-state rate equation for this mechanism predicts that the in vivo activity of the enzyme is limited by NADH product inhibition at low ethanol concentrations and by both NADH inhibition and substrate inhibition at high ethanol concentrations. When the steady-state rate equation and the measured concentrations of substrates and products in freeze-clamped liver of fed and fasted rats metabolizing alcohol are employed to calculate alcohol oxidation rates, the values agree very well with the actual rates of ethanol elimination determined in vivo.

Original languageEnglish
Pages (from-to)299-309
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume224
Issue number1
DOIs
StatePublished - Jul 1 1983

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Alcohol Dehydrogenase
Liver
Rats
Ethanol
Alcohols
Kinetics
Substrates
NAD
Enzymes
Enzyme kinetics
Metabolism
Byproducts
Fasting
Oxidation
Inhibition (Psychology)

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Steady-state kinetic properties of purified rat liver alcohol dehydrogenase : Application to predicting alcohol elimination rates in vivo. / Crabb, David; Bosron, William F.; Li, Ting Kai.

In: Archives of Biochemistry and Biophysics, Vol. 224, No. 1, 01.07.1983, p. 299-309.

Research output: Contribution to journalArticle

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