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Effects of Ethanol on Biotransformation of All‐Trans‐ Retinol and All‐Trans‐Retinal to AILTrans‐Retinoic Acid in Rat Conceptal Cytosol
Author(s) -
Chen Hao,
Namkung Moses J.,
Juchau Mont R.
Publication year - 1996
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1996.tb05275.x
Subject(s) - retinal , ethanol , retinol , retinoic acid , chemistry , cytosol , enzyme , retinoid , biochemistry , vitamin , chromatography , stereochemistry , gene
Enzymatic catalysis of the oxidations of ethanol, all‐trans‐retinol (t‐retinol) and all‐trans‐retinal (t‐retinal) were demonstrated in the cy‐tosolic fractions of rat conceptal homogenates at day 12 of gestation. Products of the retinoid oxidation reactions were identified with HPLC by comparing elution times with those of authentic standard retinoids. NAD‐dependent oxidations of each of the three substrates were demonstrable with assay conditions used t‐retinol and t‐retinal each were converted to readily detectable quantities of all‐trans‐retinoic acid (t‐RA). At 1.0 mM or higher concentrations, ethanol effectively inhibited the synthesis of t‐RA from both t‐retinol and t‐retinal when adult hepatic cytosol was used as enzyme source. Approximately 70% and 40% inhibitions, respectively, were observed at 10 mM ethanol concentrations. By contrast, for the reactions catalyzed by rat conceptal cytosol (RCC) under the same experimental conditions, ethanol failed to inhibit significantly the conversion of either t‐retinol or t‐retinal to t‐RA at concentrations up to 1,000 mM. For the RCC‐catalyzed conversion of t‐retinal to t‐RA, increasing concentrations of ethanol (0 to 1.0 M) resulted in linear increases rather than decreases in quantities of t‐RA generated. At a 2.0 M concentration of ethanol, the quantity of t‐RA increased by >50%. Significant inhibition of t‐RA generation from t‐retinal occurred only at extremely high (>4.0 M) concentrations. The results indicated that ethanol was a very ineffective inhibitor of RCC‐catalyzed synthesis of t‐RA from either t‐retinol or t‐retinal. This contrasted strongly with effective inhibitory effects with adult hepatic cytosol as enzyme source. The results supported the concept that competitive inhibition of conversion of t‐retinol to t‐RA in conceptal tissues is not a significant factor in ethanol‐elicited embryotoxicity and dysmorphogenesis, at least in rodents. Mechanisms for the eth‐anol‐induced increases in conversion of t‐retinal to t‐RA remain to be elucidated.