Oxidoreduction of butanol in deermice (Peromyscus maniculatus) lacking hepatic cytosolic alcohol dehydrogenase.
In view of conflicting information in the literature regarding enzyme systems responsible for alcohol oxidation in deermice previously reported to lack hepatic alcohol dehydrogenase (ADH) activity, the reversibility of butanol oxidation was studied in vivo and in liver-perfusion systems. Mixtures of [1,1-2H2]ethanol and butanol were given intraperitoneally to deermice lacking (ADH-) or possessing (ADH+) ADH activity, followed by analysis of alcohols in blood by GC/MS. 2H exchange between the two alcohols was seen in all experiments. In ADH- deermice, the 2H excess of butanol increased steadily and reached 18 +/- 5% after 2.5 h. In ADH+ deermice, butanol was rapidly eliminated and the 2H excess was about 7% after 0.5 h. In similar experiments with rats, the 2H excess was about 40% for 2 h. Perfusions of livers from ADH- deermice with mixtures of unlabelled and 1-[2H]butanol showed significant but slow intermolecular hydrogen transfer at C1, indicating oxidoreduction catalyzed by a dehydrogenase. Slow reduction of butanal was observed in mitochondria from ADH- deermice. ADH activity with a pH optimum of 10 and Km for ethanol of 6 mM was detected in the inner mitochondrial membranes from rats and deermice. However, low rates of oxidation observed in experiments carried out with perfused livers and in vitro suggest that this enzyme system does not contribute significantly to alcohol oxidation in vivo. Thus, perfused liver from ADH- deermice appears to be a useful system for studies of ADH-independent oxidation of alcohols. The 2H exchange between the alcohols seen in vivo indicates that both ethanol and butanol are substrates for a common extrahepatic dehydrogenase in ADH- deermice.
Cronholm
T
T
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Norsten-Höög
C
C
Ekström
G
G
Handler
J A
JA
Thurman
R G
RG
Ingelman-Sundberg
M
M
D000426:Alcohol Dehydrogenase / Q000172:deficiency*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000440:Butanols / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D000431:Ethanol / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D010542:Peromyscus; D051381:Rats; D011919:Rats, Inbred Strains
D000447:Aldehydes; D000440:Butanols; D000431:Ethanol; D000426:Alcohol Dehydrogenase; C018475:butyraldehyde