Increased hepatic retinal dehydrogenase activity after phenobarbital and ethanol administration.
Cytosolic retinal dehydrogenase (EC 1.2.1.36, retinal: NAD+ oxidoreductase) activity was measured by assessing the conversion of retinal to retinoic acid by HPLC. In vitro, acetaldehyde, chloral hydrate and disulfiram were found to be inhibitors, whereas 95% of the activity remained in the presence of cyanide or in the absence of oxygen. In rats, retinal dehydrogenase activity prevailed over that of retinal oxidase. By contrast, in deermice, 80% of retinal oxidation was due to the oxidase rather than the retinal dehydrogenase activity in a normal strain (ADH+) as well as in one lacking alcohol dehydrogenase (ADH-). In ADH- deermice, retinal oxidase activity was greater than in ADH+ animals. In vivo, in the rat, chronic ethanol administration resulted in a significant increase of the dehydrogenase activity in the liver, but not in other tissues. After phenobarbital administration, hepatic retinal dehydrogenase activity was increased 8-fold, but no extrahepatic induction was observed. Conversely, feeding rats with a diet devoid of the precursor for the substrate (retinal) by replacing retinyl acetate with an equivalent amount of retinoic acid resulted in decreased retinal dehydrogenase activity. Under conditions in which retinal dehydrogenase activity is rate-limiting for the metabolism of retinal to retinoic acid, its induction after phenobarbital or ethanol administration may contribute to hepatic vitamin A depletion.
Leo
M A
MA
Section of Liver Disease and Nutrition, Veterans Administration Medical Center, Bronx, NY 10468.
Kim
C I
CI
Lowe
N
N
Lieber
C S
CS
D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
D014801:Vitamin A; D000431:Ethanol; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde; D010634:Phenobarbital