| Evidence for the stereoselective inhibition of chick embryo hepatic ferrochelatase by N-alkylated porphyrins. | |
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MedLine Citation:
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PMID: 2811858 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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3,5-Diethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4-ethylpyridine and its 4-propyl analogue were administered to phenobarbital-pretreated rats. The N-alkylprotoporphyrins (N-alkylPPs) that were isolated from rat livers, viz., N-ethylPP and N-propylPP, were found to have greater ferrochelatase-inhibitory potency than the corresponding synthetic N-alkylPPs. The N-ethylPP that was isolated from rat liver was found to contain 72% of the NB plus NA regioisomers, whereas synthetic N-ethylPP contained 40% of the NB plus NA regioisomers. In contrast, the N-propylPP that was isolated from rat liver contained the same amount of the NB/A regioisomer(s) as synthetic N-propylPP (33%). The NB plus NA regioisomers of N-ethylPP and the NB/A regioisomer(s) of N-propylPP that were isolated from rat liver were found to be significantly more potent than the corresponding synthetic regioisomers. We conclude that 1) the ferrochelatase-inhibitory potency of N-ethylPP that is isolated from rat liver is greater than that of synthetic N-ethylPP, due to differences in both regioisomer composition and the inhibitory potency of the NB plus NA regioisomers and stereoisomers, and 2) the ferrochelatase-inhibitory potency of N-propylPP that is isolated from rat liver is greater than that of synthetic N-propylPP, due solely to the difference in the ferrochelatase-inhibitory potency of the NB/A regioisomer(s) and stereoisomers. From the enhanced ferrochelatase-inhibitory potency of the NB plus NA regioisomers of N-ethylPP and the NB/A regioisomer(s) of N-propylPP that were isolated from rat liver, relative to the corresponding synthetic N-alkyllPP regioisomers, it was inferred that 2- and 4-vinyl substituents located on pyrrole rings A and B contribute to the optimal binding of N-alkylPPs to the ferrochelatase active site. |
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Authors:
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S A McCluskey; R A Whitney; G S Marks |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular pharmacology Volume: 36 ISSN: 0026-895X ISO Abbreviation: Mol. Pharmacol. Publication Date: 1989 Oct |
Date Detail:
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Created Date: 1989-11-24 Completed Date: 1989-11-24 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 608-14 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Queen's University, Kingston, Ontario, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkylation Animals Chick Embryo Chromatography, High Pressure Liquid Circular Dichroism Ferrochelatase / antagonists & inhibitors* Liver / enzymology* Lyases / antagonists & inhibitors* Phenobarbital / pharmacology Porphyrins / biosynthesis, chemical synthesis, pharmacology* Stereoisomerism Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Porphyrins; 50-06-6/Phenobarbital; EC 4.-/Lyases; EC 4.99.1.1/Ferrochelatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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