Title : Loss of rat liver microsomal cytochrome P-450 during methimazole metabolism. Role of flavin-containing monooxygenase.

Pub. Date : 1985 Jan-Feb

PMID : 2858378






9 Functional Relationships(s)
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1 Loss of rat liver microsomal cytochrome P-450 during methimazole metabolism. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
2 The role of flavin-containing monooxygenase (FMO) in the decrease in cytochrome P-450 content during the microsomal metabolism of methimazole (N-methyl-2-mercaptoimidazole) was investigated by heat inactivation of FMO. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
3 The role of flavin-containing monooxygenase (FMO) in the decrease in cytochrome P-450 content during the microsomal metabolism of methimazole (N-methyl-2-mercaptoimidazole) was investigated by heat inactivation of FMO. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
4 Incubation of liver microsomes from untreated Fischer 344 rats with NADPH and methimazole resulted in a 25% loss of cytochrome P-450 detectable as its ferrous-carbon monoxide complex. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
5 The same extent of cytochrome P-450 loss was observed with 1 and 20 mM methimazole, suggesting saturation of the process. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
6 These results indicate that FMO-catalyzed metabolism of methimazole is necessary for the loss of cytochrome P-450 in microsomes from untreated rats. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
7 There was no loss of cytochrome P-450 when glutathione was included in the incubation with methimazole, suggesting that cytochrome P-450 loss was due to an interaction with oxygenated metabolites of methimazole formed by FMO. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
8 Losses of cytochrome P-450 were also observed after incubation of microsomes from phenobarbital- (31%) of beta-naphthoflavone-pretreated rats (44%) with NADPH and methimazole. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
9 These results indicate that both phenobarbital and beta-naphthoflavone induce isozymes of cytochrome P-450 capable of directly activating methimazole. Methimazole cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus