Effect of cholesta-3,5-dien-7-one on human liver aldehyde dehydrogenase.
A recently isolated cholesterol oxidation product, cholesta-3,5-dien-7-one, which was present at high concentrations in fatty/cirrhotic alcoholic liver was identified as a potent endogenous inhibitor of the cytosolic, E1, isozyme of aldehyde dehydrogenase (EC 1.2.1.3). The oxysterol was a less potent inhibitor of mitochondrial, E2, isozyme. The inhibition of the E1 isozyme was irreversible on the IEF gels, upon dilution and with 33 microM 2-mercaptoethanol during activity assay. The calculated 1-50% values from the inhibition curves for the E1 isozyme were 5-10 microM and approx. 180 microM for the E2 isozyme. The E3 isozyme was not sensitive to the oxysterol. Judging from the Lineweaver-Burk plot, the inhibition of the E1 isozyme with a constant concentration of cholesta-3,5-dien-7-one (52 microM) appeared to be noncompetitive.
Ryzlak
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Waksman Institute, Rutgers, State University of New Jersey, Piscataway 08855-0759.
Ambroziak
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D000293:Adolescent; D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002775:Cholestadienols / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000201:enzymology
D002775:Cholestadienols; D007527:Isoenzymes; C071069:cholesta-3,5-dien-7-one; D002784:Cholesterol; D000444:Aldehyde Dehydrogenase