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- W2065861155 abstract "The metabolism of the β-carbolines harmine and harmol by C57/BL10 mouse liver microsomes is reported. Marked changes in apparent Michaelis-Menten kinetics and metabolite profiles were induced differentially by phenobarbitone (PB) or 3-methylcholanthrene (MC). With control or PB-induced microsomes harmine was metabolised by both high- and low-affinity reactions (app. Km = 1 and 29 μM for controls; app. Km = 1.9 and 21 μM for PB-induced). Only the high-affinity reaction occurred following MC pretreatment, induced 31-fold to Vmax = 22 nmoles·min−1·mg protein−1 (app. Km = 0.4 μM). With control or PB-induced microsomes harmine was metabolised almost exclusively by O-demethylation to harmol (3-fold induction to Vmax = 9.8 nmoles·min−1·mg protein−1, app. Km = 73 and 14 μM respectively), which was probably the low-affinity reaction of harmine metabolism. With MC-induced microsomes harmine was metabolised mainly to two unidentified yellow products, with harmol as a minor metabolite formed by a high-affinity reaction (app. Km = 0.6 μM). Control, PB- and MC-induced microsomes each metabolised harmol by a high-affinity reaction (app. Km = 0.6–1.9 μM) to unidentified metabolites. Harmol metabolism was not induced by PB, but was induced by MC (22-fold to Vmax = 11 nmoles·min−1·g protein−1): this partly explains the relative lack of net harmol production after MC induction. The unidentified MC-induced yellow metabolites of harmine were not formed via harmol. Harmine and harmol metabolism showed the characteristics of cytochrome P-450 catalysed reactions. Harmine gave Type II cytochrome P-450 binding spectra with control and PB-induced microsomes, but a high-affinity Type I spectrum (Ks = 6.5 μM) with MC-induced microsomes. Harmol gave modified Type II spectra in all cases, with again higher-affinity binding to MC-induced microsomes (Ks = 62 μM) than to control (Ks ⪢ 500 μM) or PB-induced microsomes (Ks = 500 μM)." @default.
- W2065861155 created "2016-06-24" @default.
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- W2065861155 date "1983-02-01" @default.
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- W2065861155 title "Differential effects of phenobarbitone and 3-methylcholanthrene induction on the hepatic microsomal metabolism of the β-carbolines harmine and harmol" @default.
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- W2065861155 doi "https://doi.org/10.1016/0006-2952(83)90490-2" @default.
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