Abstract:
:In vivo administration of the porphyrogenic agent allylisopropylacetamide (AIA) to phenobarbital-pretreated rats results in marked loss of hepatic cytochrome P-450 content. Using isozyme-selective functional markers, we now show that such loss reflects inactivation of several phenobarbital-inducible and constitutive isozymes. Some of the isozymes (P-450a,b,h and PB-1) are largely reparable by reconstitution with exogenous hemin, indicating that after AIA-mediated loss of their prosthetic heme, their apoprotein moieties are essentially intact and functionally reconstitutable with hemin. On the other hand, after AIA-mediated inactivation, isozymes such as cytochrome P-450p remain refractory to such repair. The cause for such intractability remains somewhat elusive since AIA-mediated alkylation of the apocytochrome, proteolytic loss of the hemoprotein, or even irreversible binding of prosthetic heme catabolites to the apocytochrome does not appear to be responsible.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Bornheim LM,Underwood MC,Caldera P,Rettie AE,Trager WF,Wrighton SA,Correia MAsubject
Has Abstractpub_date
1987-08-01 00:00:00pages
299-308issue
1eissn
0026-895Xissn
1521-0111journal_volume
32pub_type
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