Porphyrinogenic activity and ferrochelatase‐inhibitory activity of sydnones in chick embryo liver cells

FEBS Letters

de Montellano, P.R.Ortiz¹  Sutherland, E.P.²  Marks, G.S.²  Grab, L.A.¹ 

[1] Department of Pharmaceutical Chemistry, School of Pharmacy, and Liver Center, University of California, San Francisco, CA 94143, USA;Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario K7L 3N6, Canada

关键词: Porphyria Ferrochelatase N-Alkylprotophyrm Sydnone Cytochrome P-450 (Chick embryo liver);   

DOI  :  10.1016/0014-5793(86)80289-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

3-[2-(2,4,6-Trimethylphenyl)thioethyl]-4-methylsydnone was shown to be a potent porphyrinogenic agent in chick embryo liver cells. The accumulation of protoporphyrin IX was consistent with the finding that ferrochelatase activity was inhibited. 3-Benzyl-4-phenylsydnone did not inhibit ferrochelatase activity and protoporphyrin IX was found to constitute only a minor fraction of the porphyrins. These results support the idea that the porphyrinogenicity of 3-[2-(2,4,6-trimethylphenyl)thioethyl]-4-methylsydnone is due to its catalytic activation by cytochrome P-450 leading to heme alkylation and formation of N-vinylprotoporphyrin IX which inhibits ferrochelatase.

【 授权许可】

Unknown