Abstract:
:Metabolism of the pulmonary toxin, 4-ipomeanol, in microsomal preparations from rabbit liver and lung and in purified cytochrome P-450-dependent monooxygenase systems was investigated. The rate of formation of reactive electrophilic products from 4-ipomeanol was estimated by measuring covalent binding to protein or glutathione. Pulmonary microsomal preparations were much more active than hepatic preparations in mediating these reactions. Both of the rabbit pulmonary cytochrome P-450 isozymes, P-450I and P-450II, were active in the metabolism of 4-ipomeanol. In the assay for covalent binding to protein, P-450I was slightly more active than P-450II at high substrate concentrations and significantly more active at low substrate concentrations. Incubation of either isozyme with 4-ipomeanol produced two glutathione conjugates but at quite different ratios. Rates of metabolism determined by conjugate formation in the purified systems were about 3 times the rates determined by covalent binding to protein, whereas both determinations gave the same values in the microsomal preparations. The relationship between the activities of P-450I and P-450II in the metabolism of 4-ipomeanol and the pulmonary toxicity of 4-ipomeanol is discussed.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Wolf CR,Statham CN,McMenamin MG,Bend JR,Boyd MR,Philpot RMsubject
Has Abstractpub_date
1982-11-01 00:00:00pages
738-44issue
3eissn
0026-895Xissn
1521-0111journal_volume
22pub_type
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