Metabolism of acetaldehyde to acetate by rat hepatic P-450s: presence of different metabolic pathway from acetaldehyde dehydrogenase system.
NADPH-dependent activity of acetaldehyde oxidation was investigated in microsomes by assaying [14C]acetic acid produced from [14C]acetaldehyde with ion-exchange column. Rat hepatic microsomes exhibited acetaldehyde oxidation activity in the presence of NADPH. This activity was induced 2-fold by the treatment of rats with ethanol. We designated this NADPH-dependent oxidation system as microsomal acetaldehyde-oxidizing system (MAOS), to distinguish from the NAD-dependent acetaldehyde oxidation system by acetaldehyde in mitochondria and cytsol. We further investigated essential enzymes contributing to MAOS activity. Acetaldehyde oxidation activity was investigated in eight forms of purified P-450 in a reconstituted system. Cytochrome P-450 (CYP) 2E1 had the highest oxidation activity and CYP1A2 and CYP4A2 had the next highest activity. Other forms had low activity. To assess the contribution of these forms to MAOS activity, immunoblot was done. CYP2E1 was induced 2-fold by ethanol treatment, but CYP1A2 and CYP4A2 were not reflecting the MAOS activity increased by ethanol treatment. These results suggest that CYP2E1 is the essential enzyme in the MAOS of rats.
Kunitoh
S
S
Department of Public Health, Osaka City University Medical School, Japan.
Asai
H
H
Imaoka
S
S
Funae
Y
Y
Monna
T
T
D000079:Acetaldehyde / Q000493:pharmacokinetics*; D000085:Acetates / Q000493:pharmacokinetics*; D019342:Acetic Acid; D000445:Aldehyde Oxidoreductases / Q000502:physiology*; D000818:Animals; D002852:Chromatography, Ion Exchange; D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000145:classification / Q000502:physiology*; D004790:Enzyme Induction / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000502:physiology; D010088:Oxidoreductases / Q000502:physiology; D010089:Oxidoreductases, N-Demethylating / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D042926:Cytochrome P-450 CYP4A; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+); D010089:Oxidoreductases, N-Demethylating; D000079:Acetaldehyde; D019342:Acetic Acid