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 (greater than or equal to 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. (C) 1997 Elsevier Science Inc.