Retinoic acid metabolism by a system reconstituted with cytochrome P-450.
Feeding rats with a diet containing a hundred times the normal amount of vitamin A resulted, within 2 to 3 weeks, in an increase in total hepatic microsomal cytochrome P-450 content. This was associated, in isolated microsomes, with an enhanced conversion of all-trans-retinoic acid to polar metabolites, including a two- to threefold increased production of 4-hydroxy- and 4-oxo-retinoic acid, whether expressed per microsomal protein or per cytochrome P-450. Unlike effects of other inducers (e.g., phenobarbital or methylcholanthrene), activities of benzphetamine, aminopyrine, and ethylmorphine demethylases or benzopyrene hydroxylase were not increased. Furthermore, the CO-reduced difference spectral peak was shifted towards 449 nm. On sodium dodecyl sulfate-gel electrophoresis, one band was increased with electrophoretic mobility identical to that of cytochrome P-450f, a recently isolated new form which has a CO-reduced difference spectral peak at 448 nm. In a system reconstituted with NADPH-cytochrome P-450 reductase, NADPH, and phospholipid, purified cytochromes P-450f and b were discovered to promote conversion of retinoic acid to polar metabolites, including 4-hydroxy-retinoic acid.
D000818:Animals; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004032:Diet; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000494:pharmacology*
D014801:Vitamin A; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System