Properties of Adlehyde Dehydrogenase from Chemically-Induced Rat Hepatomas and Normal Rat Liver
The subcellular distribution and properties of four aldehyde dehydrogenase isozymes (I–IV) identified in 2-acetylaminofluoreneinduced rat hepatomas and three aldehyde dehydrogenases (I–III) identified in normal rat liver are compared. In normal liver, mitochondria (50%) and microsomes (27%) possess the majority of the aldehyde dehydrogenase (AlDH), with cytosol possessing little activity. Isozymes I–III can be identified in both fractions and can be differentiated on the basis of substrate and coenzyme specificity, substrate Km, inhibition by disulfiram and anti-hepatoma aldehyde dehydrogenase sera, and/or isoelectric point. Hepatomas possess considerable cytosolic AlDH (20%), in addition to mitochon drial (23%) and microsomal (35%) activity. Although isozymes I–III are present in tumor mitochondria and microsomes, little isozyme I or II is found in cytosol. Hepatoma cytosolic AlDH is composed (50%) of a hepatoma-specific isozyme (IV), differing in several properties from isozymes I–III; the remainder of the tumor cytosolic activity is due to isozyme III (48%). The data indicate that expression of the tumor-specific aldehyde dehydrogenase phenotype requires both qualitative and quantitative changes involving cytosolic and microsomal aldehyde dehydrogenase. The qualitative change requires the derepression of a gene for an aldehyde dehydrogenase expressed in normal liver only following exposure to potentially harmful xenobiotics. The quantitative change involves both an increase in activity and change in subcellular location of a basal, normal liver AlDH isozyme.
KeywordsNormal Liver Subcellular Distribution Aldehyde Dehydrogenase Coenzyme Specificity Aldehyde Dehydrogenase Activity
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