Effects of riboflavin on the dimethylnitrosamine demethylase system in the rat liver

The effects of riboflavin on the dimethylnitrosamine [(DMN) CAS: 62-75-9; N-nitrosodimethylamine] demethylase system in inbred F344 rat liver were investigated. Dietary riboflavin deficiency markedly stimulated the activity of DMN demethylase I operating at a low substrate concentration (4 mM), but it caused no change in the activity of DMN demethylase II operating at a high substrate concentration (200 mM). This effect could be reversed by short-term supplementation of the vitamin by a series of three ip injections (0.5 mg/dose/day) to the deficient animals. This dosage regimen of riboflavin did not change the activity of DMN demethylase I in the normal animals. The study in vitro demonstrated that flavins were inhibitory to DMN demethylase I. The enzyme activity in the microsomes of both control and deficient animals was inhibited by preincubation with flavins, suggesting that the interaction between flavins and the enzyme rendered the enzyme inactive. Flavin adenine dinucleotide (FAD) appeared to have a more pronounced effect than riboflavin. In agreement with the earlier observation, DMN demethylase II was unaffected by FAD or riboflavin.