Studies on the metabolism of dimethylnitrosamine in vitro by rat-liver preparations. II. Inhibition by substrates and inhibitors of monoamine oxidase.
1. The metabolism of dimethylnitrosamine (DMN) to formaldehyde by rat-hepatic postmitochondrial supernatant fractions has been compared with the activities of several cytochrome P-450-dependent mixed-function oxidase enzymes and the Ziegler mixed-function amine oxidase enzyme (EC 1.14.13.8). 2. A variety of monoamine oxidase (MAO, EC 1.4.3.4) inhibitors of diverse chemical structure inhibited the metabolism of DMN. In parallel studies a number of MAO substrates, but not their deaminated products, also inhibited DMN metabolism, whereas substrates of diamine oxidase were ineffective. 3. At concentrations which inhibited DMN metabolism several MAO substrates and inhibitors did not inhibit the N-oxidation of N, N-dimethylaniline and an inhibitor and an activator of the Ziegler enzyme had no corresponding effect on DMN metabolism. 4. The metabolism of DMN and a number of MAO enzyme activities were stable to storage under conditions where mixed-function oxidase enzymes were not. 5. These results are consistent with the suggestion that DMN may, at least in part, be metabolized by hepatic enzyme(s) not dependent on cytochrome P-450 and that a microsomal amine oxidase enzyme, unrelated to the Ziegler enzyme, may be involved in the hepatic degradation of this nitrosamine. The present data does, however, suggest a role for microsomal NADPH-cytochrome c reductase in hepatic DMN metabolism.
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D004128:Dimethylnitrosamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D008996:Monoamine Oxidase Inhibitors; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors; C019668:amine oxidase, mixed function; D004128:Dimethylnitrosamine