Acetaldehyde as a substrate for ethanol-inducible cytochrome P450 (CYP2E1).
Liver microsomes from starved and acetone-treated rats catalyzed NADPH-supported metabolism of acetaldehyde at a rate 8-fold higher than corresponding control microsomes; the Vmax was about 6 nmol/mg microsomal protein/min and the apparent Km 30 microM. The reaction was efficiently inhibited by anti-CYP2E1 IgG, but not by control IgG. Reconstituted membranes containing rat CYP2E1 and cytochrome b5 metabolized acetaldehyde with a Vmax of 20 nmol/nmol/min and an apparent Km of 30 microM, whereas CYP2B4 containing vesicles or vesicles without b5 were ineffective. Gas chromatographic/mass spectrometric analysis of products formed from [2H4]-acetaldehyde with CYP2E1-containing reconstituted membrane vesicles revealed the formation of acetate as the only detectable product, although other water soluble products were also formed as evidenced from incubations with [1,2-14C]acetaldehyde. The results indicate that CYP2E1 is an aldehyde oxidase and thus metabolizes both ethanol and its primary oxidation product. This might have implications in vivo for acetaldehyde metabolism in liver and brain.
Terelius
Y
Y
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Norsten-Höög
C
C
Cronholm
T
T
Ingelman-Sundberg
M
M
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D000431:Ethanol; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; C583129:cytochrome P-450 CYP2B4, rat; D000079:Acetaldehyde; D010634:Phenobarbital