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Interaction of chemicals with cytochrome P-450: implications for the porphyrinogenicity of drugs.

Abstract：

:Our studies lead us to suggest that in order for an organic chemical to cause porphyrin accumulation in chick embryo hepatocyte culture, it must be: 1. lipophilic; 2. resistant to biotransformation by phase I or phase II reactions to compounds which are devoid of biological activity; and 3. capable of interacting with cytochrome P-450 with concomitant destruction of the heme moiety or the generation of reactive oxygen species. The interaction of porphyrin-inducing chemicals with cytochrome P-450 results in lowering of a regulatory "free heme" pool. The "free heme" pool may be lowered by inhibiting one or more of the enzymes of heme biosynthesis or by destruction of the heme moiety of cytochrome P-450. Specific chemical features enable organic chemicals to inhibit ferrochelatase activity or to destroy the heme moiety of cytochrome P-450. Chemicals with a wide variety of structures are able to inhibit uroporphyrinogen decarboxylase activity.

journal_name

Clin Biochem

journal_title

Clinical biochemistry

authors

Marks GS,McCluskey SA,Mackie JE,Riddick DS,James CA

doi

10.1016/s0009-9120(89)80073-6

subject

Has Abstract

pub_date

1989-06-01 00:00:00

pages

169-75

issue

3

eissn

0009-9120

issn

1873-2933

pii

S0009-9120(89)80073-6

journal_volume

22

pub_type

杂志文章

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