Interactions of heterocyclic Maillard products with the hepatic microsomal monooxygenase system

1. Interactions of methyl-substituted pyrazines, and other constituents of Maillard products generated during heat treatment of food, with hepatic microsomal mixed-function oxygenases were studied in vitro. 2. Spectral interactions of N-containing heteroaromatic compounds with the cytochrome P-450 system are type I or type II depending on the state of induction, and are relatively weak. Inhibition of 7-ethoxycoumarin O-deethylation by these compounds is ten times lower than that of metyrapone, agreeing with the weak spectral interaction. Inhibition is competitive for 2,3-dimethylquinoxaline, and complex for 2,5-dimethylpyrazine and 2,3,5,6-tetramethylpyrazine. 3. Spectral and inhibitory interactions indicate biotransformation. This was studied with 2,3,5,6-tetramethylpyrazine; the metabolite formed was identified as 2-hydroxymethyl-3,5,6-trimethylpyrazine. Metabolism to the N-oxide did not occur.