Ethanol-metabolizing pathways in deermice. Estimation of flux calculated from isotope effects

Journal Article · Fri Jun 05 00:00:00 EDT 1987 · J. Biol. Chem.; (United States)

OSTI ID:6465424

Alderman, J; Takagi, T; Lieber, C S

The apparent deuterium isotope effects on Vmax/Km (D(V/K) of ethanol oxidation in two deermouse strains (one having and one lacking hepatic alcohol dehydrogenase (ADH) were used to calculate flux through the ADH, microsomal ethanol-oxidizing system (MEOS), and catalase pathways. In vitro, D(V/K) values were 3.22 for ADH, 1.13 for MEOS, and 1.83 for catalase under physiological conditions of pH, temperature, and ionic strength. In vivo, in deermice lacking ADH (ADH-), D(V/K) was 1.20 +/- 0.09 (mean +/- S.E.) at 7.0 +/- 0.5 mM blood ethanol and 1.08 +/- 0.10 at 57.8 +/- 10.2 mM blood ethanol, consistent with ethanol oxidation principally by MEOS. Pretreatment of ADH- animals with the catalase inhibitor 3-amino-1,2,4-triazole did not significantly change D(V/K). ADH+ deermice exhibited D(V/K) values of 1.87 +/- 0.06 (untreated), 1.71 +/- 0.13 (pretreated with 3-amino-1,2,4-triazole), and 1.24 +/- 0.13 (after the ADH inhibitor, 4-methylpyrazole) at 5-7 mM blood ethanol levels. At elevated blood ethanol concentrations (58.1 +/- 2.4 mM), a D(V/K) of 1.37 +/- 0.21 was measured in the ADH+ strain. For measured D(V/K) values to accurately reflect pathway contributions, initial reaction conditions are essential. These were shown to exist by the following criteria: negligible fractional conversion of substrate to product and no measurable back reaction in deermice having a reversible enzyme (ADH). Thus, calculations from D(V/K) indicate that, even when ADH is present, non-ADH pathways (mostly MEOS) participate significantly in ethanol metabolism at all concentrations tested and play a major role at high levels.

• Research Organization: Veterans Administration Medical Center, Bronx, NY
• OSTI ID: 6465424
• Journal Information: J. Biol. Chem.; (United States), Vol. 16
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ALCOHOL DEHYDROGENASE
ENZYME ACTIVITY
CATALASE
ETHANOL
METABOLISM
ACETATES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
DEUTERIUM
ISOTOPE EFFECTS
LIVER
RATS
ALCOHOLS
ANIMALS
BODY
CARBOXYLIC ACID SALTS
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HEMIACETAL DEHYDROGENASES
HYDROGEN ISOTOPES
HYDROXY COMPOUNDS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PEROXIDASES
REACTION KINETICS
RODENTS
STABLE ISOTOPES
VERTEBRATES
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