Biotransformation of all-trans-retinal, 13-cis-retinal, and 9-cis-retinal catalyzed by conceptal cytosol and microsomes.
Oxidative conversions of all-trans-retinal (t-RAL), 13-cis-retinal (13-cRAL), and 9-cis-retinal (9-cRAL) to their corresponding retinoic acids (RAs) catalyzed by rat conceptal cytosol (RCC) or microsomes (RCM) were studied. The primary product of RCC-catalyzed oxidations of both t-RAL and 13-cRAL was t-RA, with only trace amounts of 13-cRA and 9-cRA. In the RCC-catalyzed oxidation of 9-cRAL, generated t-RA, 9-cRA, and 13-cRA constituted approximately 56, 34, and 10%, respectively, of the total RAs. For all RCC-catalyzed retinal oxidations, NAD was a much more effective cofactor than NADP. And t-RAL and 13-cRAL were much better substrates than 9-cRAL. Formaldehyde, acetaldehyde, citral, and disulfiram were investigated as inhibitors, but only citral and disulfiram effectively inhibited the RCC-catalyzed conversion of t-RAL or 13-cRAL to t-RA. Methanol and ethanol failed to inhibit either reaction even at very high concentrations (> or = 10 mM). RCM exhibited lower specific enzymatic activities than RCC in catalyzing oxidations of t-RAL, 13-cRAL, and 9-cRAL, indicating that the cytosolic fraction was dominant for converting retinals to RAs. The predominant RA produced from RCM-catalyzed oxidations of t-RAL, 13-cRAL, or 9-cRAL was t-RA for each substrate, and again NAD was a much more effective cofactor than NADP in all cases. For RCM-catalyzed oxidations of RALs, 13-cRAL was a much better substrate than t-RAL or 9-cRAL. Methanol and ethanol were not effective inhibitors for RCM-catalyzed oxidations of t-RAL or 13-cRAL. In RCM-catalyzed reactions, citral (10 mM) completely inhibited oxidation of t-RAL but showed only a minor effect on oxidation of 13-cRAL. 13-cRA was converted almost completely to t-RA after 2 hr of incubation with RCC.
Chen
H
H
Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195, USA.
Juchau
M R
MR
D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000648:ultrastructure; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D008861:Microsomes / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012172:Retinaldehyde / Q000378:metabolism*; D013237:Stereoisomerism
D000431:Ethanol; D012172:Retinaldehyde