Effects of induction on the metabolism and cytochrome P-450 binding of harman and other beta-carbolines.
1. The metabolism of harman by liver microsomes from non-induced, phenobarbitone (PB)-induced and 3-methylcholanthrene (MC)-induced mice was investigated. Initial reaction rates for harman disappearance were measured and showed a 4-fold induction by PB and a 10.6-fold induction by MC. 2. The major metabolite formed with each microsomal preparation was identified as 6-hydroxyharman. 3. Microsomal cytochrome P-450 binding was measured for harman and other beta-carbolines and both Type I and Type II binding spectra were observed, being dependent upon the mode of induction.
Tweedie
D J
DJ
Department of Biochemistry, University of Louisville, School of Medicine, Ky 40292.
Prough
R A
RA
Burke
M D
MD
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D002243:Carbolines / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D013053:Spectrophotometry
D000470:Alkaloids; D002243:Carbolines; D006247:Harmine; D008748:Methylcholanthrene; C005010:harman; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital