The formation of an N-hydroxymethyl intermediate in the N-demethylation of N-methylcarbazole in vivo and in vitro.
1. The metabolism of N-methylcarbazole has been studied in several mammalian species, both in vivo and in vitro. 2. An important metabolite after incubation of N-methylcarbazole with liver microsomes in vitro was identified as N-hydroxymethylcarbazole. 3. This metabolite was also found as a conjugate (probably the O-glucuronide) in the urine of some species. 4. N-Hydroxymethylcarbazole decomposed spontaneously in solution at pH 7-4 to formaldehyde and carbazole; this breakdown was enhanced by incubation with liver microsomes from several species, especially the guinea-pig. 5. The role of N-methyl hydroxylation, compared with N-oxidation, in the mechanism of N-dealkylation of non-basic N-methyl compounds is discussed.
D000818:Animals; D002227:Carbazoles / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D002227:Carbazoles; D010089:Oxidoreductases, N-Demethylating