Enhancement of microsomal aniline and acetanilide hydroxylation by haemoglobin.
1. Haemogloblin and myoglobin enhance rat liver microsomal p-hydroxylation of aniline and acetanilide. Microsomal N-demethylation of ethylmorphine and aminopyrine is not increased by haemoproteins. 2. The enhancement of microsomal p-hydroxylation is maximal at high substrate concentration and high haeme compound concentration. 3. Detergent-purified NADPH-cytochrome c reductase, free flavins and manganese ions considerably increase the haemoglobin-mediated, tissue-free hydroxylation of aniline. Microsomal aniline hydroxylation is not enhanced by haeme, ferric ion or albumin. 4 Catalase and cyanide ions are powerful inhibitors of haemoglobin-mediated aniline hydroxylation both in the presence and absence of tissue. Carbon monoxide inhibits the hydroxylase activity of the tissue-free system to a smaller extent than that of a system containing microsomes plus haemoglobin whereas p-chloromercuribenzoate inhibits only the flavoprotein-dependent hydroxylation of aniline mediated by haemoglobin. 5. Several possibilities of interactions between substrate, microsomes and haeme compounds are proposed.
D000083:Acetanilides / Q000378:metabolism*; D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000815:Aniline Hydroxylase / Q000378:metabolism*; D000818:Animals; D003579:Cytochrome Reductases / Q000378:metabolism*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism*; D006454:Hemoglobins / Q000494:pharmacology*; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats
D000083:Acetanilides; D006454:Hemoglobins; D006899:Mixed Function Oxygenases; D000815:Aniline Hydroxylase; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D005037:Ethylmorphine-N-Demethylase; D003579:Cytochrome Reductases; D009251:NADPH-Ferrihemoprotein Reductase