thiobenzamide and Ascorbic-Acid-Deficiency

Activity of the flavin-containing monooxygenase (FMO) was reduced significantly in ascorbic acid deficient guinea pigs. Reduction in oxidation of dimethylaniline (DMA) and of thiobenzamide was associated with a decrease in the activity of the FMO. In both ascorbate supplemented and deficient guinea pig hepatic 12,000 g supernatant fractions, SKF-525A and n-octylamine did not inhibit DMA N-oxidation. Phenobarbital pretreatment did not increase the rate of N-oxidation of DMA. In addition, hepatic supernatant fractions thermally treated at 50 degree were unable to N-oxidize DMA, but 80% of the cytochrome P-450 activity was retained. Also, N-oxidation of DMA was reduced by 53% at pH 7.0, while oxidation of cytochrome P-450 specific substrates was inhibited by only 19%. Kinetic studies of DMA N-oxidation indicate no significant change in the apparent Km in ascorbate supplemented or deficient animals. The in vitro addition of ascorbic acid had no effect on the activity of the FMO. The toxicological implications of the reduction in FMO activity in ascorbic acid deficiency are discussed.

Topics: Aminopyrine N-Demethylase; Aniline Compounds; Aniline Hydroxylase; Animals; Ascorbic Acid Deficiency; Cytochrome b Group; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Cytochrome-B(5) Reductase; Cytochromes b5; Guinea Pigs; Hot Temperature; Hydrogen-Ion Concentration; Kinetics; Male; Oxidation-Reduction; Oxygenases; Thioamides