In vitro O-demethylation from a heterocyclic nitrogen: a novel metabolic reaction?
1. O-Demethylation of 1-methoxyindole-3-carboxylic acid, in vitro, by determination of liberated formaldehyde, has been demonstrated using fortified 15,000 g rat liver supernatant fraction. 2. Results have been compared to those similarly obtained with a standard O-demethylation substrate, 4-nitroanisole, to substantiate and quantify the extent of the reaction. 3. Km values for 4-nitroanisole and methoxyindole-3-carboxylic acid were 8.9 and 6.5 mM, while Vmax values were 4.9, and 5.2 nmol HCHO produced/mg protein per min. 4. The significance of the metabolic O-demethylation reaction for N-methoxyindoles as a novel metabolic pathway is discussed in terms of pharmacological activity and biological reactivity.
Nwankwo
J O
JO
Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.
D000818:Animals; D000840:Anisoles / Q000378:metabolism; D005260:Female; D006571:Heterocyclic Compounds / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D010090:Oxidoreductases, O-Demethylating / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D000840:Anisoles; D006571:Heterocyclic Compounds; D007211:Indoles; C070960:1-methoxyindole-3-carboxylic acid; D010090:Oxidoreductases, O-Demethylating; C005306:4-nitroanisole